Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3

作者：Yang Rongxi^*; Chen Bowang; Pfuetze Katrin; Buch Stephan; Steinke Verena; Holinski Feder Elke; Stoecker Sarah; von schoenfels Witigo; Becker Thomas; Schackert Hans K; Royer Pokora Brigitte; Kloor Matthias; Schmiegel Wolff H; Buettner Reinhard; Engel Christoph; Puertolas Jesus Lascorz; Foersti Asta; Kunkel Nelli; Bugert Peter; Schreiber Stefan; Krawczak Michael; Schafmayer Clemens; Propping Peter; Hampe Jochen; Hemminki Kari; Burwinkel Barbara

来源：Carcinogenesis, 2014, 35(2): 315-323.

DOI：10.1093/carcin/bgt344

Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the missing heritability of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio 1.66, P 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC.

• 单位
  河北医科大学