Systematic discovery of germline cancer predisposition genes through the identification of somatic second hits

Systematic discovery of germline cancer predisposition genes through the identification of somatic second hits [1]

The genetic causes of cancer include both somatic mutations and inherited germline variants. Large-scale tumor sequencing has revolutionized the identification of somatic driver alterations but has had limited impact on the identification of cancer predisposition genes (CPGs). Here we present a statistical method, ALFRED, that tests Knudson’s two-hit hypothesis to systematically identify CPGs from cancer genome data. Applied to ~10,000 tumor exomes the approach identifies known and putative CPGs – including the chromatin modifier NSD1 – that contribute to cancer through a combination of rare germline variants and somatic loss-of-heterozygosity (LOH).

Original Source [2]

Publication Date:

04/07/2018

Author(s): Solip Park [3], Fran Supek [4], Ben Lehner [5]

Source: Nature Communications [6]

Vol:

Issue:

2601

pp:

1-13

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