Tissue-specificity in cancer: The rule, not the exception

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Science  15 Mar 2019:
Vol. 363, Issue 6432, pp. 1150-1151
DOI: 10.1126/science.aaw3472


We are in the midst of a renaissance in cancer genetics. Over the past several decades, candidate-based targeted sequencing efforts provided a steady stream of information on the genetic drivers for certain cancer types. However, with recent technological advances in DNA sequencing, this stream has become a torrent of unbiased genetic information revealing the frequencies and patterns of point mutations and copy number variations (CNVs) across the entire spectrum of cancers. One of the most important observations from this work is that genetic alterations in bona fide cancer drivers (those genes that, when mutated, promote tumorigenesis) show a remarkable spectrum of tissue specificity: Alterations in certain driver genes appear only in cancers derived from one or a few tissue types (1). Only a handful of cancer drivers [such as telomerase reverse transcriptase (TERT), TP53, the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus, and MYC] show broad tissue spectrums. Here, we discuss the concept of tissue specificity of genetic alterations in cancer and provide general hypotheses to help explain this biological phenomenon.