Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

Phenocopy
DOI: 10.1016/j.celrep.2018.03.076 Publication Date: 2018-04-05T14:55:36Z
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ABSTRACT
<h2>Summary</h2> DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 types. Mutations with accompanying loss heterozygosity were observed in over 1/3 genes, including <i>TP53</i> <i>BRCA1/2</i>. Other prevalent included epigenetic silencing the direct genes <i>EXO5</i>, <i>MGMT</i>, <i>ALKBH3</i> ∼20% samples. Homologous recombination (HRD) was present at varying frequency many types, most notably ovarian cancer. However, contrast cancer, HRD associated worse outcomes several other cancers. Protein structure-based analyses allowed us predict functional consequences rare, recurrent mutations. A new machine-learning-based classifier developed from gene expression data identify that phenocopy deleterious These frequent human cancers have may determine progression guide therapy.
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