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Chromosome 8

Human chromosome 8 is one of the 23 pairs of chromosomes in the normal human karyotype, characterized as a medium-sized metacentric chromosome that spans more than 146 million base pairs of DNA and accounts for between 4.5% and 5% of the total genetic material in cells.^[1] It encodes approximately 700 protein-coding genes, along with thousands of non-coding RNAs and pseudogenes, which collectively contribute to essential biological processes such as brain development, innate immunity, and cellular signaling.^[2] In 2021, the first complete end-to-end assembly of human chromosome 8 was achieved using long-read sequencing technologies, revealing a total length of 146,259,671 base pairs, including previously unsequenced regions like the centromere and a polymorphic β-defensin gene cluster at 8p23.1.^[3] The chromosome is divided into a shorter p arm (approximately 45 million base pairs) and a longer q arm (over 100 million base pairs), with the centromere located near the middle at 8p11-q11.^[4] Notable structural features include higher-order α-satellite repeats in the centromere, which span about 2.08 megabases and exhibit evolutionary conservation among great apes, as well as copy number variations in immune-related gene clusters that influence disease susceptibility.^[3] Key genes on chromosome 8 include MYC at 8q24, a proto-oncogene involved in cell proliferation and frequently deregulated in various cancers through translocations or amplifications.^[5] Abnormalities in chromosome 8 are associated with a range of genetic disorders and malignancies. Trisomy 8, often occurring in mosaic form, leads to developmental delays, intellectual disability, and characteristic facial features.^[1] Recombinant chromosome 8 syndrome, caused by a deletion of most of the short (p) arm and duplication of the distal long (q) arm resulting from a parental pericentric inversion, features intellectual disability, growth retardation, and congenital anomalies such as heart and urinary tract defects, while 8q deletions are linked to trichorhinophalangeal syndrome type II, characterized by skeletal and hair abnormalities.^[1] In oncology, translocations such as t(8;14)(q24;q32) drive Burkitt lymphoma by juxtaposing MYC with immunoglobulin loci, and t(8;21)(q22;q22) contributes to core binding factor acute myeloid leukemia.^[1] Additionally, copy number variations in the β-defensin cluster on 8p have been implicated in inflammatory conditions like Crohn's disease.^[6]

Overview

Physical Characteristics

Chromosome 8 is one of the 23 pairs of chromosomes found in the nucleus of human cells and is classified as an autosome, meaning it does not play a role in sex determination.^[1] It exhibits a submetacentric shape, characterized by a centromere positioned slightly off-center, which results in two arms of unequal length: a shorter p arm and a longer q arm.^[7] This morphology is visible under microscopic examination during metaphase of cell division, where the chromosome appears as a distinct, rod-like structure. The total length of chromosome 8 is approximately 146 million base pairs (Mb), accounting for about 4.5–5% of the entire human genome.^[1] The short arm (8p) measures around 45 Mb, while the long arm (8q) extends to about 101 Mb, with the centromere separating these regions at roughly the 45 Mb mark from the p-arm telomere.^[8]^[9] The centromere of chromosome 8 is a specialized heterochromatic region composed primarily of higher-order α-satellite DNA repeats, forming a 2.08 Mb array known as D8Z2, which is AT-rich and flanked by monomeric α-satellite sequences on the p arm.^[9] Constitutive heterochromatin is concentrated at this centromeric core, as well as at the telomeric ends of both the p and q arms, contributing to the chromosome's structural stability and compaction.^[9] These heterochromatic distributions are typical of human chromosomes and aid in maintaining integrity during replication and segregation.

Functional Role

Chromosome 8, as one of the 22 autosomes in the human genome, plays a fundamental role in the transmission of genetic material across generations by being inherited as a pair—one copy from each parent—in diploid somatic cells.^[1] This paired structure ensures the balanced inheritance of autosomal genetic information during gamete formation and fertilization, maintaining the diploid state essential for human development and cellular function.^[10] In cellular processes, chromosome 8 is critical for normal DNA replication and cell division. During the S phase of the cell cycle, the DNA comprising chromosome 8 duplicates to form sister chromatids, preparing for equitable distribution to daughter cells.^[10] This replication process, coupled with the chromosome's submetacentric configuration—with the centromere positioned slightly off-center—facilitates efficient packaging and alignment on the mitotic spindle, supporting accurate segregation during mitosis to preserve genomic integrity in proliferating somatic cells.^[11] Furthermore, chromosome 8 contributes to overall genome stability through its role in maintaining proper gene dosage in diploid cells, where the presence of two homologous copies prevents imbalances that could disrupt cellular homeostasis.^[10] In meiosis, the chromosome's structure enables homologous pairing and recombination, ensuring haploid gametes receive a single intact copy, which is vital for genetic diversity and stable inheritance. Its relatively large size, spanning approximately 146 million base pairs, influences chromatin compaction, aiding in the orderly progression of meiotic divisions without compromising fidelity.^[1]^[11]

Genomic Structure

Cytogenetic Banding

Cytogenetic banding of chromosome 8 refers to the visualization of its characteristic light and dark patterns under light microscopy, which aids in chromosome identification and abnormality detection during karyotyping. Chromosome 8 is submetacentric, featuring a shorter p arm and a longer q arm separated by the centromere. The G-banding pattern on the short arm (8p) includes major bands from 8p23 distally to 8p11 proximally, such as 8p23, 8p22, 8p21, 8p12, and 8p11, with the p arm typically displaying two dark bands that may appear somewhat unclear. On the long arm (8q), bands extend from 8q11 near the centromere to 8q24 at the telomere, encompassing prominent regions like 8q11, 8q12, 8q13, 8q21, 8q22, 8q23, and 8q24, where two to three dark bands are visible, the most distal one being notably intense.^[12]^[13]^[14] G-banding, the most common technique for this visualization, involves treating fixed metaphase chromosomes with trypsin to partially digest proteins and expose differential staining sites, followed by staining with Giemsa solution, which binds preferentially to AT-rich DNA regions to produce dark G-positive bands while leaving GC-rich areas as light G-negative bands.^[15] This method reflects underlying chromatin differences, with dark bands corresponding to late-replicating, gene-poor regions and light bands to early-replicating, gene-rich areas. Routine G-banding of chromosome 8 achieves a resolution of 400-550 bands per haploid set, sufficient to resolve structural features and alterations larger than 5-10 megabases.^[16] In clinical practice, the cytogenetic banding pattern of chromosome 8 is essential for karyotype analysis, enabling the detection of structural abnormalities such as interstitial deletions, duplications, or balanced/unbalanced translocations that may disrupt chromosomal integrity.^[17] These banding features provide a foundational tool for identifying potential chromosomal imbalances, which are further explored in sections on associated conditions.

Sequence Assembly

The initial assembly of human chromosome 8 as part of the Human Genome Project, completed in 2003, covered over 90% of the genome but left substantial gaps, particularly in heterochromatic and highly repetitive regions such as centromeres and segmental duplications.^[18] A subsequent finished sequence of the euchromatic portion was published in 2006, spanning approximately 145 million base pairs, yet unresolved gaps persisted in pericentromeric and telomeric areas due to limitations in short-read sequencing technologies. Significant progress toward a complete assembly occurred in 2021 with the first telomere-to-telomere (T2T) sequence of chromosome 8, achieved using complementary long-read technologies including ultra-long Oxford Nanopore Technologies (ONT) reads and Pacific Biosciences (PacBio) HiFi sequencing.^[9] This assembly spans 146,259,671 bases, adding 3,334,256 unique bases beyond the prior GRCh38 reference, and fully resolves previous gaps in repetitive regions.^[9] This chromosome 8 assembly contributed to the 2022 T2T-CHM13 telomere-to-telomere human genome reference, which includes a complete sequence of chromosome 8 and serves as a current standard as of 2025.^[19] Key milestones include the complete resolution of the centromeric alpha-satellite array, a 2.08 Mb D8Z2 higher-order repeat (HOR) structure that is heavily methylated except for a 73-kb hypomethylated region within a 632-kb CENP-A chromatin domain.^[9] Long-read sequencing also enabled the precise assembly of challenging repetitive loci, such as the beta-defensin gene cluster at 8p23.1, resolving it into a 7.06 Mb region and eliminating two 50 kb gaps from GRCh38.^[9] These advancements provide a gapless reference for future genomic studies, highlighting the role of advanced sequencing in overcoming the limitations of earlier assemblies.^[9]

Genetic Content

Gene Count and Density

Human chromosome 8 harbors approximately 710 protein-coding genes, based on annotations from Ensembl and GENCODE releases up to 2025.^[20]^[21] In addition to these, the chromosome includes thousands of non-coding RNA genes, pseudogenes, and other genetic elements such as regulatory RNAs, bringing the total annotated gene count to over 2,400.^[22] This represents roughly 3.6% of the human genome's approximately 19,400 protein-coding genes overall.^[23] Gene density on chromosome 8 is lower than the genomic average, at about 5 genes per megabase (Mb), compared to the approximately 6-7 protein-coding genes per Mb across the euchromatic human genome. Spanning roughly 146 Mb, the chromosome exhibits uneven distribution, with higher gene clustering in euchromatic bands such as 8q and 8p regions, while heterochromatic pericentromeric areas show reduced density.^[1] The complete telomere-to-telomere assembly of chromosome 8, published in 2021, added over 3 million bases previously missing from GRCh38, identifying 61 new protein-coding genes and 33 new non-coding genes in gapped regions like the β-defensin cluster at 8p23.1, including 12 new protein-coding loci in that cluster from long-read transcriptomics.^[9]

Key Genes

Chromosome 8 harbors several genes with critical roles in cellular processes, including the proto-oncogene MYC located at band 8q24. The MYC gene encodes a nuclear phosphoprotein that functions as a transcription factor, regulating cell cycle progression, apoptosis, and cellular transformation by activating and repressing numerous target genes involved in proliferation and growth.^[24] Another prominent gene on chromosome 8 is NRG1 (neuregulin 1) at 8p12, which encodes a signaling protein that mediates cell-cell interactions and plays a key role in neural development by promoting the growth and differentiation of neurons and glial cells through activation of ErbB receptor tyrosine kinases.^[25] Adjacent to NRG1 at 8p12 is GSR (glutathione reductase), which encodes an enzyme that catalyzes the reduction of glutathione disulfide to the sulfhydryl form glutathione, thereby maintaining cellular redox balance and supporting antioxidant defense mechanisms essential for protecting against oxidative stress. The ANK1 gene, situated at 8p11.21, produces ankyrin-1, a cytoskeletal protein that anchors the spectrin-actin network to the plasma membrane in red blood cells, thereby ensuring membrane stability and structural integrity during cellular deformation. At the telomeric region 8p23.1 lies MCPH1 (microcephalin 1), which encodes a protein involved in brain development through regulation of centrosome duplication, chromosome condensation, and DNA damage response pathways that coordinate cell division and genomic integrity.^[26]

Associated Conditions

Chromosomal Abnormalities

Chromosomal abnormalities of chromosome 8 encompass numerical and structural variants that disrupt the normal genetic balance, often arising de novo or through parental inheritance, and are detectable through cytogenetic and molecular techniques. These alterations can lead to partial monosomy or trisomy of specific regions, resulting in developmental and physical challenges. Partial deletions of the short arm, particularly involving the 8p23.1 to pter region (monosomy 8p), are among the more frequently reported structural changes, with affected individuals exhibiting growth deficiency and congenital malformations such as heart defects and diaphragmatic issues.^[27]^[28] Duplications of chromosome 8, including partial trisomy 8p and supernumerary ring chromosomes derived from chromosome 8, represent gain-of-function abnormalities that typically cause intellectual disability and developmental delays. Trisomy 8p involves duplication of the short arm, leading to a highly variable phenotype that may include facial dysmorphisms and motor impairments, while supernumerary ring chromosomes 8 often occur in mosaic form and contribute to cognitive challenges without consistent loss of subtelomeric sequences.^[29]^[30] Translocations involving chromosome 8 are structural rearrangements that exchange genetic material with other chromosomes, commonly observed in hematologic conditions; for instance, the t(8;21)(q22;q22) translocation fuses parts of chromosomes 8 and 21 and occurs in approximately 5-12% of acute myeloid leukemia cases. Isochromosomes of chromosome 8, such as i(8q) or i(8p), are rare mirror-image duplications that result in trisomy of one arm and monosomy of the other, though they are infrequently documented outside specific disease contexts.^[31]^[32] Detection of these abnormalities relies on techniques like fluorescence in situ hybridization (FISH) for targeted locus analysis and array comparative genomic hybridization (array CGH) for high-resolution mapping of copy number variations. 8p deletions are rare chromosomal abnormalities with clinical significance in prenatal and postnatal diagnostics.^[33]^[34]

Genetic Disorders

Langer-Giedion syndrome, also known as trichorhinophalangeal syndrome type II (TRPS II), is a rare contiguous gene deletion disorder caused by a microdeletion at 8q24.11-q24.13 that encompasses the TRPS1 and EXT1 genes.^[35] This deletion leads to characteristic clinical features including sparse scalp hair, bulbous nasal tip, thin upper lip, intellectual disability, short stature, and multiple bony exostoses, with skeletal abnormalities such as cone-shaped epiphyses and hip dysplasia.^[35] The syndrome overlaps significantly with TRPS II, sharing the same genetic etiology and manifesting similar craniofacial and skeletal dysmorphisms, though exostoses are more prominent in Langer-Giedion cases due to EXT1 haploinsufficiency.^[36] Inheritance is autosomal dominant, but most cases arise de novo, with rare familial transmission reported.^[35] Diagnosis typically involves clinical evaluation of dysmorphic features followed by chromosomal microarray analysis or fluorescence in situ hybridization to confirm the 8q deletion.^[35] Recombinant chromosome 8 syndrome, also called rec(8) syndrome or San Luis Valley syndrome, results from a recombinant chromosome 8 with duplication of 8q22.1→qter and deletion of 8p23.1→pter, often originating from malsegregation during meiosis in a parent carrying a pericentric inversion of chromosome 8 (inv(8)(p23.1q22.1)).^[37] Affected individuals exhibit a distinctive phenotype including moderate to severe intellectual disability, postnatal growth retardation, facial anomalies such as hypertelorism, anteverted nares, and a thin upper lip, as well as congenital heart defects (e.g., tetralogy of Fallot in approximately 40% of cases) and genitourinary malformations.^[37] The condition is more prevalent in individuals of Hispanic descent from the San Luis Valley region due to a founder effect.^[37] Inheritance follows an autosomal dominant pattern with a parental carrier risk of about 6.2% for an affected offspring, higher in maternal transmissions.^[37] Diagnosis is established through karyotyping or chromosomal microarray to identify the specific duplication-deletion pattern.^[37] Hereditary spherocytosis type 1 (HS1) is an inherited hemolytic anemia primarily caused by mutations in the ANK1 gene at 8p11.21, which encodes erythroid ankyrin-1, a key protein for red blood cell membrane stability.^[38] These mutations, including missense, nonsense, and frameshift variants, disrupt ankyrin function, leading to spherical red blood cells with increased fragility, resulting in symptoms such as chronic hemolytic anemia, jaundice, splenomegaly, and gallstone formation.^[38] Unlike deletion syndromes, HS1 does not involve large-scale chromosomal changes but rather point mutations or small insertions/deletions.^[38] The disorder is typically autosomal dominant with variable expressivity, though recessive forms occur with compound heterozygous mutations; de novo mutations are infrequent but possible.^[38] Diagnosis relies on peripheral blood smear showing spherocytes, osmotic fragility testing, and confirmatory genetic sequencing of ANK1.^[38] These disorders highlight the diverse clinical impacts of chromosome 8 alterations, with genetic testing essential for precise diagnosis and counseling, often revealing de novo events in structural variants.^[35]^[37]^[38]

Cancer Associations

Oncogenic Regions

Chromosome 8 exhibits several recurrent alterations that contribute to oncogenesis, with gains on the long arm (8q) being among the most frequent aneuploidies observed across various solid tumors, including prostate and breast cancers.^[39] These gains often involve amplification of specific subregions, leading to overexpression of oncogenes and promotion of tumor progression. In particular, 8q gain has been reported in approximately 30-70% of prostate cancer cases, depending on disease stage, with higher frequencies in advanced or hormone-refractory tumors.^[40]^[41] A key oncogenic hotspot is the 8q24 region, which contains long-range enhancer elements that regulate the nearby MYC proto-oncogene, a well-known driver of cell proliferation and survival. Amplification of 8q24 is common in solid tumors and results in enhanced MYC expression through these non-coding regulatory sequences located in a gene desert.^[5] This alteration is implicated in multiple cancer types due to its role in disrupting normal transcriptional control of MYC.^[42] In contrast, losses on the short arm, particularly at 8p23, involve deletions in the beta-defensin gene cluster, which encodes antimicrobial peptides with potential tumor-suppressive functions. The human beta-defensin 1 (DEFB1) gene in this region acts as a candidate tumor suppressor, and its cancer-specific loss through homozygous deletion or epigenetic silencing promotes tumor development.^[43] These deletions are frequently associated with loss of heterozygosity (LOH), a mechanism that inactivates the remaining allele and eliminates suppressive activity.^[44] The primary mechanisms driving these oncogenic changes include chromosomal amplification, which increases gene dosage and leads to oncogene overexpression, such as MYC at 8q24, and LOH at 8p, which results in biallelic inactivation of tumor suppressors like DEFB1. These alterations often arise from chromosomal instability, including breakage-fusion-bridge cycles or isochromosome formation, contributing to the selective advantage of cancer cells.^[45]^[46]

Specific Malignancies

Chromosome 8 alterations are implicated in several specific malignancies, primarily through translocations, amplifications, or gains that dysregulate key oncogenes such as MYC and FGFR1, or create fusion proteins like RUNX1-ETO. These genetic changes drive tumorigenesis by enhancing proliferation, inhibiting differentiation, and promoting survival pathways in affected cell types.^[47] In Burkitt lymphoma, the most common chromosomal abnormality is the translocation t(8;14)(q24;q32), which juxtaposes the MYC proto-oncogene at 8q24 with the immunoglobulin heavy chain locus (IGH) at 14q32, leading to constitutive MYC overexpression under the control of immunoglobulin enhancers.^[48] This translocation occurs in approximately 75-80% of sporadic and endemic cases, resulting in rapid B-cell proliferation and lymphomagenesis.^[49] Variant translocations t(2;8) or t(8;22) involving light chain loci are less frequent but similarly activate MYC.^[50] Acute myeloid leukemia (AML) with maturation (FAB M2 subtype) frequently features the t(8;21)(q22;q22) translocation, fusing the RUNX1 (also known as AML1) gene on chromosome 21q22 with the RUNX1T1 (formerly ETO) gene on 8q22 to produce the RUNX1-ETO fusion protein.^[31] This fusion acts as a transcriptional repressor, blocking normal myeloid differentiation and promoting leukemic stem cell self-renewal, and is found in 5-12% of AML cases overall.^[51] The presence of this fusion often correlates with a favorable response to standard chemotherapy, though additional mutations can worsen outcomes.^[47] The 8p11 myeloproliferative syndrome (EMS), a rare and aggressive stem cell disorder, arises from various translocations at 8p11 that fuse the FGFR1 tyrosine kinase gene with partner genes, leading to ligand-independent receptor activation and constitutive signaling through downstream pathways like PI3K/AKT and MAPK.^[52] Over 15 such fusions have been identified, including t(8;13)(p11;q12) with FGFR1OP1/ZNF198 and t(8;22)(p11;q11) with BCR, resulting in an initial myeloproliferative phase that rapidly progresses to acute leukemia in most patients.^[53] EMS typically presents with eosinophilia and monocytosis, distinguishing it from other myeloproliferative neoplasms.^[54] In prostate cancer, gains or amplifications of the 8q24 region, encompassing the MYC locus, are observed in up to 50% of advanced tumors and strongly correlate with disease progression, higher Gleason scores, and increased risk of metastasis.^[55] These copy number alterations drive MYC overexpression, which disrupts androgen receptor signaling and promotes epithelial-to-mesenchymal transition, facilitating tumor invasion.^[56] Such 8q24 gains serve as an independent predictor of biochemical recurrence post-prostatectomy.^[57] Prognostic implications of chromosome 8 alterations vary by malignancy; for instance, t(8;21) in AML is generally associated with better overall survival compared to other cytogenetic risks, while 8q24 gains in prostate cancer predict poorer outcomes and higher metastatic potential.^[47] In EMS, the rapid progression to blast crisis confers a dismal prognosis without allogeneic stem cell transplantation, with median survival under 18 months.^[52] Targeted therapies are emerging, particularly for MYC-driven cancers; FGFR1 inhibitors like ponatinib have shown activity in EMS by blocking fusion kinase signaling, achieving responses in preclinical models and early clinical cases.^[58] For MYC-dependent malignancies like Burkitt lymphoma, small-molecule inhibitors such as CX-5461 (a POLR1 inhibitor indirectly targeting MYC) and devimistat (CPI-613) are in phase I/II trials, demonstrating complete remissions in relapsed/refractory settings with manageable toxicity.^[59] As of 2025, at least five MYC-targeted agents are under evaluation in oncology trials, emphasizing combination strategies to overcome MYC's undruggability.^[60]

Evolutionary Aspects

Comparative Genomics

Human chromosome 8 exhibits high synteny with its orthologous chromosome 8 in other primates, particularly great apes, reflecting the close evolutionary relationship among these species. Comparative analyses reveal that the overall structure of human chromosome 8 is largely conserved with chimpanzee chromosome 8, with only minor rearrangements such as small inversions and translocations in pericentromeric and telomeric regions. This conservation extends to gorillas and orangutans, where chromosome painting and marker mapping confirm shared gene order and orientation across most of the chromosome arms.^[61] The 2021 telomere-to-telomere assembly of human chromosome 8 has further illuminated these homologies, showing approximately 99% sequence identity in aligned regions with great ape orthologs, providing key insights into the genetic divergence between humans and apes that occurred around 6-7 million years ago.^[9] In contrast, synteny with rodent genomes is more fragmented due to extensive rearrangements over ~90 million years of divergence. Human chromosome 8 corresponds to segments distributed across mouse chromosomes 3, 8, and 13, with at least 10-15 synteny blocks identified through high-resolution breakpoint mapping using bacterial artificial chromosome sequences. These disruptions highlight the dynamic nature of mammalian genome evolution, where inversions, fusions, and fissions have reshaped chromosomal architecture while preserving functional gene linkages.^[62] A notable divergent feature is the β-defensin gene cluster on the short arm (8p23.1), which has undergone significant expansion in the human lineage compared to other apes, driven by segmental duplications and copy number variations linked to enhanced innate immunity.^[9] This cluster, comprising up to 40 genes in humans with polymorphic copy numbers ranging from 2 to 12, shows fewer intact copies in chimpanzees and gorillas, suggesting adaptive evolution in response to pathogen pressures unique to hominins.^[63] Orthologs of key genes on human chromosome 8, such as the proto-oncogene MYC at 8q24.21, are highly conserved across mammals, maintaining similar exon-intron structures and regulatory elements from mice to primates.^[64] This conservation underscores the essential role of MYC in cellular proliferation and development, with sequence identities exceeding 90% in coding regions even in distantly related species like rodents.

Human-Specific Elements

The complete linear assembly of human chromosome 8, achieved in 2021 using long-read sequencing technologies, revealed approximately 3.33 Mb of previously unsequenced DNA, including 12 novel protein-coding genes within the β-defensin gene cluster at 8p23.1.^[9] Among these, five additional DEFB genes (DEFB103B, DEFB104A, DEFB105A, DEFB106A, and DEFB107A) were identified in regions that were gaps in prior assemblies, contributing to immune system function through antimicrobial peptide production and associating with phenotypes such as psoriasis and Crohn's disease via copy number variations.^[9] This cluster's resolution highlights human-specific expansions in immune-related loci, potentially influencing pathogen resistance in modern populations. An inverted haplotype spanning 4.11 Mb at 8p23.1, resolved in the same assembly, predisposes to recurrent microdeletions that increase risks for congenital heart defects, microcephaly, and developmental delay, underscoring chromosome 8's role in neurodevelopmental and cardiac vulnerabilities unique to human genomic architecture.^[9] Centromeric regions of human chromosome 8 exhibit distinct CpG methylation patterns within α-satellite higher-order repeat (HOR) variants, as observed across haplotype-resolved assemblies like CHM1 and CHM13.^[65] These patterns feature hypomethylated DNA at the kinetochore site, known as the centromere dip region (CDR), which varies in position—averaging 178 kb in CHM1 versus 214 kb in CHM13—and can shift by over 500 kb between individuals, thereby modulating centromere strength and chromosomal stability through epigenetic regulation of kinetochore assembly.^[65] Such human-specific epigenetic variability in α-satellite arrays may contribute to inter-individual differences in genome integrity. Human-specific structural variants in the 8p23.1 region, including a 4.2-Mb inversion polymorphism present at frequencies of 60% in African populations and 20% in Asian populations, arise from interchromosomal core duplicons (e.g., DA/Xiao elements) that drive recurrent rearrangements.^[66] These duplications, which expanded over approximately 25 million years and include a 746-kb duplicative transposition dated to about 0.84 million years ago, facilitate evolutionary instability but also heighten disease susceptibility; for instance, microdeletions of 3.6 Mb in this region are linked to congenital heart defects, microcephaly, and developmental delay, with breakpoints often mapping to duplicon-rich segments like SD19 and SD20/21/25.^[66] Evolutionary regions on chromosome 8, particularly around 8p12, harbor the WRN gene, where biallelic loss-of-function mutations cause Werner syndrome—a premature aging disorder manifesting in adolescence with accelerated features like graying hair, cataracts, diabetes, and cancer predisposition, uniquely prevalent in human populations.^[67] Over 2,300 sequence variants in WRN have been documented in humans, many of uncertain pathogenicity but potentially modulating aging-related risks through impaired DNA repair and helicase activity, distinguishing human susceptibility from other primates.^[68] This locus exemplifies chromosome 8's contribution to human-specific aging trajectories, with no direct ortholog equivalents in non-human species exhibiting the full syndrome.^[69]

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Jun 1, 2017 · ... TRPS II are related to the loss of multiple genes on chromosome 8. The TRPS1, EXT1, and RAD21 genes are missing in people with TRPS II.
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Recombinant chromosome 8 syndrome (Rec8 syndrome) is a chromosomal disorder found among individuals of Hispanic descent with ancestry from the San Luis Valley ...
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Hereditary spherocytosis refers to a group of heterogeneous disorders that are characterized by the presence of spherical-shaped erythrocytes (spherocytes) ...
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Chromosome 8q was the most frequent gain observed in this meta-analysis dataset, with 211 of 662 (31.9%) tumors harboring extra copies of 8q. Chromosome 8q gain ...<|separator|>
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The most common genetic aberrations were losses of 8p (72.5%), 13q (50%), 1p (50%), 22 (45%), 19 (45%), 10q (42.5%), and 16q (42.5%) and gains of 8q (72.5%), 7q ...
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Jan 26, 2010 · It has been speculated that these 8q24 genetic variant(s) might affect Myc expression by altering its regulation or amplification status. Here, ...
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Human beta-defensin-1 (hBD-1) is a candidate tumor suppressor gene located on chromosome 8p23. Previously, we showed that cancer-specific loss of hBD-1 was ...
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Mar 22, 2019 · The hBD-1 gene is located at chromosome 8p23, an area that has been found repeatedly to undergo tumor-associated loss of heterozygosity.
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May 9, 2016 · Here, we created human cellular models that mimic cancer-associated chromosome 8p LOH. Although individual suppression of multiple 8p genes ...
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Aug 6, 2025 · Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic ...<|control11|><|separator|>
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The t(8;21) abnormality occurs in a minority of acute myeloid leukemia (AML) patients. The translocation results in an in-frame fusion of two genes.
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May 1, 2016 · Most Burkitt lymphoma cases show the t(8;14)(q24;q32) [MYC-IGH] and less commonly the t(8;22)(q24;q11) or t(2;8)(p12;q24).
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Abstract. The t(8;14)(q24;q32), involving MYC gene (8q24) and the immunoglobulin heavy chain (IgH) locus (14q32), represents about 75% of all translocations ...
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Around two‐thirds of the latter patients carry a t(8;14)(q24;q32) chromosomal translocation that on the molecular level fuses the MYC gene to the immunoglobulin ...
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The 8p11 myeloproliferative syndrome is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 ...
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Currently, it has been reported that 17 FGFR1 gene rearrangements exist in EMS, including 15 translocations, 1 insertion, and 1 inversion (Figure 1). Herein, we ...Introduction · Genotypic and phenotypic... · Targeted therapy with tyrosine...
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The characteristic chromosomal translocation always involves the fibroblast growth factor receptor 1 (FGFR1) gene at chromosome 8p11 [1]. Its presence in both ...
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MYC and Prostate Cancer - PMC - NIH
Because the amplification of the 8q24 region is predominantly observed in late-stage/aggressive tumors, it has been widely held that MYC is involved in disease ...
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8q24 amplification is associated with Myc expression and prostate ...
The amplified region contains the oncogene MYC that has been shown to be overexpressed at both messenger RNA and protein levels in prostate cancer [2], [5], [11] ...
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Ponatinib as targeted therapy for FGFR1 fusions associated with the ...
Ponatinib-treated cells from 8p11 myeloproliferative syndrome patients (n=5) showed reduced colony growth compared to controls.
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MYC as a Target for Cancer Treatment: from Undruggable to ... - NIH
Aug 15, 2025 · Currently, at least five anti-MYC compounds are being evaluated for potential anti-cancer activity in clinical trials. Results from a phase I ...
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NCT03793140 | A Study of CPI-613 for Patients With Relapsed or ...
Novel devimistat results in complete remissions in heavily pretreated Burkitt lymphoma in a phase 2 trial. Blood Adv. 2025 Nov 11;9(21):5556-5563. doi ...
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Human and mouse genomic sequences reveal extensive breakpoint ...
The human and mouse genomic sequences provide evidence for a larger number of rearrangements than previously thought and reveal extensive reuse of breakpoints.
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https://clinicaltrials.gov/study/NCT03793140
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Removal of evolutionarily conserved functional MYC domains in a ...
Jul 26, 2023 · MYC TF orthologs are highly conserved across many species although the N-terminal part is often more variable than the C-terminal part of MYC ...
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The variation and evolution of complete human centromeres | Nature
Apr 3, 2024 · We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks ...
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Recurrent rearrangements of Chromosome 8p23.1 are associated with congenital heart defects and developmental delay. The complexity of this region has led to ...
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Werner syndrome - Genetics - MedlinePlus
Feb 24, 2022 · Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging.
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Werner syndrome - UpToDate
Oct 20, 2025 · The human WRN gene displays abundant genetic variation. Nearly 2300 sequence variants in or within 75 base pairs of a WRN coding exon were ...
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Genetic and Epigenetic Insights into Werner Syndrome
Feb 14, 2025 · Werner syndrome is an autosomal recessive disorder characterized by premature aging and cancer predisposition, caused by loss of function mutations in WRN gene.