Statistical Bioinformatics Webinar: Castro -- Cancer Mutation Differences Between Men and Women

Presented by Ms.  Andrea Castro, PhD Student, University of California at San Diego 

Cancer is a heterogenous disease, largely initiated and driven by genomic alterations.
Some of these alterations can be detected by immune surveillance, leading the adaptive
immune system to attack tumor cells.  Indeed, immune evasion is one of the hallmark
behaviors shared by all cancers.  The major histocompatibility complexes (MHC) are
central to immune surveillance, determining which of the genomic alterations in tumor
cells can be presented to T cells.  The peptide binding region of MHC-I is encoded by
the highly polymorphic HLA genes (HLA-A/B/C) which ultimately determine peptide-MHC
specificities.  Tumor cells with "invisible" mutations escape immune surveillance
whereas cells with "visible" mutations are more likely to be recognized and eliminated
by T cells.  Several studies have found that tumor genome landscapes show a bias for
mutations that are "invisible" to the MHC.  To better understand the factors that
influence host anti-tumor immunity, we studied tumor mutation landscapes in the TCGA and
found that mutation landscapes from tumors occurring in younger and female individuals
are more depleted of "visible" mutations, suggesting that a stronger immune system may
produce stronger constraints on tumor evolution.  Furthermore, loss of integrity of the
MHC is reflected by an excess of well-presented mutations.  These findings have
implications for developing effective immunotherapies.