Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer

Kouji Banno, Nobuyuki Susumu, Takeshi Hirao, Megumi Yanokura, Akira Hirasawa, Daisuke Aoki, Yasuhiro Udagawa, Kokichi Sugano, Shiro Nozawa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). This cancer is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. The present study was undertaken to analyze the relation between microsatellite instability (MSI) and germline mutations of MMR genes. We analyzed MSI in 38 cases of endometrial cancer. MSI was present in one or more (out of 5 examined) regions in 11 (29%) cases. Furthermore, alterations in MLH1 and MSH2, two culprit genes representative of HNPCC, were examined in the 11 MSI-positive patients using polymerase chain reaction-single-strand conformation polymorphism and sequencing. Germline mutations, namely, 1) a missense mutation at codon 688 (ATG→ATA, Met→Ile) and 2) a missense mutation at codon 390 (CTT→TTT, Leu→Phe) of the MSH2 gene, were found in 2 of the 11 patients (18%). Although these two cases do not fulfill the new Amsterdam criteria, they had strong family histories of colorectal and endometrial carcinoma. Our results show that genetic testing is important in cases of endometrial cancer with a history suggestive of HNPCC even if the new Amsterdam criteria are not fulfilled.

Original languageEnglish
Pages (from-to)58-65
Number of pages8
JournalCancer Genetics and Cytogenetics
Volume146
Issue number1
DOIs
Publication statusPublished - Oct 1 2003
Externally publishedYes

Fingerprint

Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Endometrial Neoplasms
Germ-Line Mutation
Mutation
DNA Mismatch Repair
Missense Mutation
Codon
Genes
Genetic Testing
Colorectal Neoplasms
Neoplasms
History
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer. / Banno, Kouji; Susumu, Nobuyuki; Hirao, Takeshi; Yanokura, Megumi; Hirasawa, Akira; Aoki, Daisuke; Udagawa, Yasuhiro; Sugano, Kokichi; Nozawa, Shiro.

In: Cancer Genetics and Cytogenetics, Vol. 146, No. 1, 01.10.2003, p. 58-65.

Research output: Contribution to journalArticle

Banno, Kouji ; Susumu, Nobuyuki ; Hirao, Takeshi ; Yanokura, Megumi ; Hirasawa, Akira ; Aoki, Daisuke ; Udagawa, Yasuhiro ; Sugano, Kokichi ; Nozawa, Shiro. / Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer. In: Cancer Genetics and Cytogenetics. 2003 ; Vol. 146, No. 1. pp. 58-65.
@article{8aef629acb4841dc94e2c1d6ec07b6e9,
title = "Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer",
abstract = "Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). This cancer is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. The present study was undertaken to analyze the relation between microsatellite instability (MSI) and germline mutations of MMR genes. We analyzed MSI in 38 cases of endometrial cancer. MSI was present in one or more (out of 5 examined) regions in 11 (29{\%}) cases. Furthermore, alterations in MLH1 and MSH2, two culprit genes representative of HNPCC, were examined in the 11 MSI-positive patients using polymerase chain reaction-single-strand conformation polymorphism and sequencing. Germline mutations, namely, 1) a missense mutation at codon 688 (ATG→ATA, Met→Ile) and 2) a missense mutation at codon 390 (CTT→TTT, Leu→Phe) of the MSH2 gene, were found in 2 of the 11 patients (18{\%}). Although these two cases do not fulfill the new Amsterdam criteria, they had strong family histories of colorectal and endometrial carcinoma. Our results show that genetic testing is important in cases of endometrial cancer with a history suggestive of HNPCC even if the new Amsterdam criteria are not fulfilled.",
author = "Kouji Banno and Nobuyuki Susumu and Takeshi Hirao and Megumi Yanokura and Akira Hirasawa and Daisuke Aoki and Yasuhiro Udagawa and Kokichi Sugano and Shiro Nozawa",
year = "2003",
month = "10",
day = "1",
doi = "10.1016/S0165-4608(03)00157-2",
language = "English",
volume = "146",
pages = "58--65",
journal = "Cancer Genetics and Cytogenetics",
issn = "0165-4608",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Identification of germline MSH2 gene mutations in endometrial cancer not fulfilling the new clinical criteria for hereditary nonpolyposis colorectal cancer

AU - Banno, Kouji

AU - Susumu, Nobuyuki

AU - Hirao, Takeshi

AU - Yanokura, Megumi

AU - Hirasawa, Akira

AU - Aoki, Daisuke

AU - Udagawa, Yasuhiro

AU - Sugano, Kokichi

AU - Nozawa, Shiro

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). This cancer is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. The present study was undertaken to analyze the relation between microsatellite instability (MSI) and germline mutations of MMR genes. We analyzed MSI in 38 cases of endometrial cancer. MSI was present in one or more (out of 5 examined) regions in 11 (29%) cases. Furthermore, alterations in MLH1 and MSH2, two culprit genes representative of HNPCC, were examined in the 11 MSI-positive patients using polymerase chain reaction-single-strand conformation polymorphism and sequencing. Germline mutations, namely, 1) a missense mutation at codon 688 (ATG→ATA, Met→Ile) and 2) a missense mutation at codon 390 (CTT→TTT, Leu→Phe) of the MSH2 gene, were found in 2 of the 11 patients (18%). Although these two cases do not fulfill the new Amsterdam criteria, they had strong family histories of colorectal and endometrial carcinoma. Our results show that genetic testing is important in cases of endometrial cancer with a history suggestive of HNPCC even if the new Amsterdam criteria are not fulfilled.

AB - Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). This cancer is caused by germline mutations in one of the DNA mismatch repair (MMR) genes. The present study was undertaken to analyze the relation between microsatellite instability (MSI) and germline mutations of MMR genes. We analyzed MSI in 38 cases of endometrial cancer. MSI was present in one or more (out of 5 examined) regions in 11 (29%) cases. Furthermore, alterations in MLH1 and MSH2, two culprit genes representative of HNPCC, were examined in the 11 MSI-positive patients using polymerase chain reaction-single-strand conformation polymorphism and sequencing. Germline mutations, namely, 1) a missense mutation at codon 688 (ATG→ATA, Met→Ile) and 2) a missense mutation at codon 390 (CTT→TTT, Leu→Phe) of the MSH2 gene, were found in 2 of the 11 patients (18%). Although these two cases do not fulfill the new Amsterdam criteria, they had strong family histories of colorectal and endometrial carcinoma. Our results show that genetic testing is important in cases of endometrial cancer with a history suggestive of HNPCC even if the new Amsterdam criteria are not fulfilled.

UR - http://www.scopus.com/inward/record.url?scp=0141565164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141565164&partnerID=8YFLogxK

U2 - 10.1016/S0165-4608(03)00157-2

DO - 10.1016/S0165-4608(03)00157-2

M3 - Article

C2 - 14499697

AN - SCOPUS:0141565164

VL - 146

SP - 58

EP - 65

JO - Cancer Genetics and Cytogenetics

JF - Cancer Genetics and Cytogenetics

SN - 0165-4608

IS - 1

ER -