HLA-A

Overview

HLA-A encodes a classical MHC class I molecule critical for antigen presentation to CD8+ T cells. In HGSOC precursor lesions, HLA-A is upregulated as part of an early IFN-driven immune response.

Alterations observed in the corpus

  • HLA-A is significantly upregulated beginning at the p53 signature stage in HGSOC fallopian tube precursors, as part of IFN-alpha and IFN-gamma pathway activation (including STAT1, IFITM1, IRF9, IRF7, ISG15, TAP1); upregulation persists through STIC and invasive cancer PMID:39386723.
  • In STIC.C and invasive cancer epithelial cells, HLA-A is co-expressed with MX1, defining a classical antigen-presentation program active in late-stage lesions PMID:39386723.
  • Epigenetically silenced via promoter hypermethylation and focal deletions in breast cancer metastases; correlated with reduced HLA-A protein expression (Spearman rho=0.6, P=0.0001) and lower immune cell infiltrates PMID:36585450
  • MHC class I gene highly expressed in HGSOC Cancer.cell.3 cluster; subject to LOH-mediated loss in 6p as immune escape mechanism PMID:36517593
  • HLA-A is recurrently mutated in DLBCL by whole-exome sequencing of 55 tumors (MutSig analysis, Broad Institute) PMID:22343534
  • Nonsense/splice-site loss-of-function mutations in 7 of 8 mutated cases; novel finding in lung squamous cell carcinoma (TCGA, 178 tumors); one of 10 significantly mutated genes (FDR q < 0.1); implicated in immune evasion; relevant to immunotherapy patient selection PMID:22960745
  • Significantly mutated in 3% of HNSCC; immune-evasion role; implicated alongside B2M in antigen presentation pathway alterations (7% HPV(-), 11% HPV(+)) PMID:25631445
  • 96 somatic HLA class I (HLA-A/B/C) mutations in 11% of colorectal cancer cases; biased toward exon 4 (TCR-binding domain) and peptide-contact residues in exons 2-3; mutated alleles carry more neoantigens than non-mutated alleles (Wilcoxon p=0.006) PMID:26997480
  • B2M focally deleted in both lung ADC and SqCC, enriched for loss-of-function mutations (Pan-Lung FDR q=0.006); HLA-A/B implicated in MHC-I antigen presentation loss in TCGA pan-lung cancer cohort PMID:27158780
  • Antigen-presentation gene profiled in OncoPrint alongside JAK1/JAK2/JAK3, POLE, CD274, PTEN, and ATR in a 240-patient NSCLC immunotherapy cohort; targeted panels were noted to lack comprehensive HLA coverage, motivating future panel expansion PMID:29337640

Cancer types (linked)

  • HGSOC — upregulated from p53 signature precursor stage onward as part of early IFN signaling; potential biomarker for risk stratification of precursor lesions PMID:39386723.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • IFN pathway activation including HLA-A upregulation in precursor lesions could serve as early detection biomarker for high-risk HGSOC patients; no direct therapeutic target reported PMID:39386723.

Open questions

  • Whether classical MHC-I upregulation (HLA-A) and non-classical MHC-I upregulation (HLA-E) have additive vs. competing roles in immune shaping of HGSOC precursors is unresolved PMID:39386723.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36585450

This page was processed by crosslinker on 2026-05-14. - PMID:36517593

This page was processed by crosslinker on 2026-05-14. - PMID:22343534

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:26997480

This page was processed by wiki-cli on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:29337640

This page was processed by wiki-cli on 2026-05-15.