2017
DOI: 10.1016/j.cell.2017.10.001
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Abstract: SummaryImmune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and … Show more

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Cited by 959 publications
(805 citation statements)
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“…Passenger mutations, defined as mutations occurring only 1-2 times across all tumors in non-cancer genes, had a PHBR-II score distribution very similar to that of random mutations with an enrichment for PHBR-II scores near 0, suggesting that many passengers are likely to be effectively presented. This enrichment of presented passenger mutations is consistent with recent reports that HLA loss of heterozygosity is frequent in some tumor types (Chowell et al, 2017; McGranahan et al, 2017; Ryschich et al, 2004) and is associated with the accumulation of mutations that would have been effectively presented by the lost allele (McGranahan et al, 2017). Consequently, 25% percent of the passenger mutation PHBR-II scores fall below the PHBR-II cutoff of 6 (Figure 3D).…”
Section: Resultssupporting
confidence: 92%
“…Passenger mutations, defined as mutations occurring only 1-2 times across all tumors in non-cancer genes, had a PHBR-II score distribution very similar to that of random mutations with an enrichment for PHBR-II scores near 0, suggesting that many passengers are likely to be effectively presented. This enrichment of presented passenger mutations is consistent with recent reports that HLA loss of heterozygosity is frequent in some tumor types (Chowell et al, 2017; McGranahan et al, 2017; Ryschich et al, 2004) and is associated with the accumulation of mutations that would have been effectively presented by the lost allele (McGranahan et al, 2017). Consequently, 25% percent of the passenger mutation PHBR-II scores fall below the PHBR-II cutoff of 6 (Figure 3D).…”
Section: Resultssupporting
confidence: 92%
“…Previous work has reported loss of heterozygosity (LOH) of HLA-I genes in cancer (43, 44). We thus analyzed all tumor exomes from cohort 1 and identified 32 patients who were heterozygous at all HLA-I loci but had LOH in at least one HLA-I locus in their tumors (table S1).…”
mentioning
confidence: 99%
“…In addition, low‐grade glioma showed an exacerbated diversity in ITH after treatment with the alkylating agent temozolomide 39. In non‐small‐cell lung cancers (NSCLC) and bladder cancer, the apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like (APOBEC) family of proteins was associated with fostering many subclones (signature 2) 19, 20, 40…”
Section: General Components Of Ithmentioning
confidence: 99%
“…Losing the ability to present neoantigens, as a result of human leukocyte antigen (HLA) loss, may facilitate immune evasion. McGranahan et al40 reported that HLA loss of heterozygosity (LOH) occurs in 40% of NSCLC. LOH is an immune escape mechanism that is subject to strong microenvironment later in tumor evolution.…”
Section: Clonal Selective Factors For Fostering Ithmentioning
confidence: 99%