Systematic search for rare variants in Finnish early-onset colorectal cancer patients

Cancer Genetics
Tomas TanskanenLauri A Aaltonen

Abstract

The heritability of colorectal cancer (CRC) is incompletely understood, and the contribution of undiscovered rare variants may be important. In search of rare disease-causing variants, we exome sequenced 22 CRC patients who were diagnosed before the age of 40 years. Exome sequencing data from 95 familial CRC patients were available as a validation set. Cases with known CRC syndromes were excluded. All patients were from Finland, a country known for its genetically homogenous population. We searched for rare nonsynonymous variants with allele frequencies below 0.1% in 3,374 Finnish and 58,112 non-Finnish controls. In addition, homozygous and compound heterozygous variants were studied. No genes with rare loss-of-function variants were present in more than one early-onset CRC patient. Three genes (ADAMTS4, CYTL1, and SYNE1) harbored rare loss-of-function variants in both early-onset and familial CRC cases. Five genes with homozygous variants in early-onset CRC cases were found (MCTP2, ARHGAP12, ATM, DONSON, and ROS1), including one gene (MCTP2) with a homozygous splice site variant. All discovered homozygous variants were exclusive to one early-onset CRC case. Independent replication is required to associate the discovered varian...Continue Reading

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Citations

Jun 10, 2016·Cellular Oncology (Dordrecht)·M M HahnA Geurts van Kessel
Sep 14, 2016·Psychiatry Research·Patricia GassóJosefina Castro-Fornieles
Oct 8, 2016·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Laura Valle
Feb 24, 2016·PLoS Genetics·Richarda M de VoerRoland P Kuiper
Dec 12, 2019·Inflammation·Haiyan XueFengxue Zhu
May 16, 2019·Cellular and Molecular Life Sciences : CMLS·Sipin ZhuJiake Xu
Jun 27, 2020·Journal of Clinical Medicine·Mariona TerradasLaura Valle
Nov 25, 2020·International Journal of Molecular Sciences·Iris B A W Te PaskeRicharda M de Voer
Dec 13, 2019·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Anthony M MusolfJoan E Bailey-Wilson
May 30, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Melissa RotunnoElizabeth M Gillanders
Jul 16, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·B DalmassoUNKNOWN MelaNostrum consortia

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