Germline Mutation of RPS20, Encoding a Ribosomal Protein, Causes Predisposition to Hereditary Nonpolyposis Colorectal Carcinoma Without DNA Mismatch Repair Deficiency

被引：152

作者：

Nieminen, Taina T. ^{[1
]}

O'Donohue, Marie-Francoise ^{[6
,7
]}

Wu, Yunpeng ^{[8
]}

Lohi, Hannes ^{[2
,3
,9
,10
]}

Scherer, Stephen W. ^{[11
,12
,13
,14
]}

Paterson, Andrew D. ^{[11
,12
]}

Ellonen, Pekka ^{[4
]}

Abdel-Rahman, Wael M. ^{[1
,6
,15
]}

Valo, Satu ^{[1
,5
]}

Mecklin, Jukka-Pekka ^{[16
,17
]}

Jarvinen, Heikki J. ^{[18
]}

Gleizes, Pierre-Emmanuel ^{[6
,7
]}

Peltomaki, Paivi ^{[1
]}

机构：

[1] Univ Helsinki, Haartman Inst, Dept Med Genet, FI-00014 Helsinki, Finland

[2] Univ Helsinki, Fac Med, Res Programs Unit, Helsinki, Finland

[3] Univ Helsinki, Fac Vet Med, Dept Vet Biosci, Helsinki, Finland

[4] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

[5] Univ Helsinki, Dept Biosci, Helsinki, Finland

[6] Univ Toulouse, UPS, Lab Biol Mol Eucaryote, Toulouse, France

[7] CNRS, UMR 5099, Toulouse, France

[8] Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA

[9] OU HCOM, Dept Specialty Med, Athens, OH USA

[10] Folkhalsan Inst Genet, Helsinki, Finland

[11] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada

[12] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada

[13] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada

[14] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[15] Univ Sharjah, Coll Hlth Sci, Dept Med Lab Sci, Sharjah, U Arab Emirates

[16] Jyvaskyla Cent Hosp, Dept Surg, Jyvaskyla, Finland

[17] Univ Eastern Finland, Inst Clin Med, Kuopio, Finland

[18] Univ Helsinki, Cent Hosp, Dept Surg 2, Helsinki, Finland

来源：

GASTROENTEROLOGY | 2014年 / 147卷 / 03期

基金：

欧洲研究理事会;

关键词：

Colon Cancer; Hereditary Nonpolyposis Colorectal Cancer; Ribosome; Exome Sequencing; LYNCH-SYNDROME; CANCER; HNPCC; MSH6; MLH1; RNA;

D O I：

10.1053/j.gastro.2014.06.009

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Little is known about the genetic factors that contribute to familial colorectal cancer type X (FCCX), characterized by hereditary nonpolyposis colorectal carcinoma with no mismatch repair defects. Genetic linkage analysis, exome sequencing, tumor studies, and functional investigations of 4 generations of a FCCX family led to the identification of a truncating germline mutation in RPS20, which encodes a component (S20) of the small ribosomal subunit and is a new colon cancer predisposition gene. The mutation was associated with a defect in pre-ribosomal RNA maturation. Our findings show that mutations in a gene encoding a ribosomal protein can predispose individuals to microsatellite-stable colon cancer. Evaluation of additional FCCX families for mutations in RPS20 and other ribosome-associated genes is warranted.

引用

页码：595 / +

页数：9

共 25 条

[1]

Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations [J].