Not all genomic mutations are expressed at the transcript/
protein level, which may explain variation in
cancer development, prognosis, and treatment response/resistance. In this study, our aim was to describe the prevalence of somatic mutation loss of expression ('variant silencing') in a large collection of human samples, and the potential impact of such variant silencing on
tumor immunogenicity. Whole-exome mutation description and
tumor-normal paired
mRNA expression data originating from 636 unique patients diagnosed with 21 distinct
tumor types (all solid
tumors) were retrieved from The
Cancer Genome Atlas (TCGA). Antigenicity and immunogenicity of neopeptides originating from mutated
proteins within a same
tumor sample were predicted using the tools available from the Immune
Epitope Database (IEDB). A total of 65,072 missense mutations were studied. We demonstrated that 9.06% (N = 10,604 silenced/117,505 total variants) somatic variants were silenced in human
tumors. Transciptomic silencing is significantly associated with
proteins presenting better
peptide processing, MHC-I binding, and T-cell recognition; and is more likely observed in lymphocyte-depleted
tumors. Silencing may participate in
tumor resistance by clonal selection and immune evasion. In the era of
precision medicine, we suggest that therapeutic choices should be informed by both the presence of a genomic mutation and its actual transcript expression.