Lic. Biotecnologia

Cancer Genetics and Cytogenetics 182 (2008) 136e139

Short communication

A novel missense MSH2 gene mutation in a patient of a Korean
family with hereditary nonpolyposis colorectal cancer
Seo-Jin Parka, Kyung-A Leea, Tae Sung Parka, Nam Kyu Kimb, Jaewoo Songa,
Bo-Young Kimc, Jong Rak Choia,*
a

Department of Laboratory Medicine, Yonsei University College of Medicine, 250 Seongsanno,Seodaemun-gu, Seoul 120-752, Korea
b
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
c
Department of Molecular Genetics, Seoul Medical Science Institute, Seoul, Korea
Received 3 December 2007; accepted 13 January 2008

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer-susceptible
syndrome that predisposes to the earlydevelopment of colorectal cancer. Germline mutations in
DNA mismatch repair genes, particularly MLH1 and MSH2, are associated with the clinical phenotype of HNPCC. A previously unreported, novel missense mutation in exon 3 of the MSH2 gene
(c.380AOT) was identified in the proband and a different missense mutation in exon 3 of MSH2
gene (c.505AOG) was noted in the mother, with a mutual splicemutation in intron 12 of the
MSH2 gene in the proband, mother, and younger brother. Here, we report the clinical implications
of a novel mutation in a patient with early-onset colorectal cancer and the significance of a common
underlying splice site mutation occurring within a family with HNPCC. Ó 2008 Elsevier Inc. All
rights reserved.

1. Introduction

2. Materials and methods

Hereditarynonpolyposis colorectal cancer (HNPCC) is
one of the most common hereditary cancer-susceptible syndromes; it has an autosomal dominant inheritance pattern
and predisposes to the early development of colorectal cancer, as well as malignancies of the endometrium, ovaries,
stomach, small bowel, hepatobiliary tract, and urinary tract
[1,2]. The Bethesda criteria were produced to overcome
some of thelimitations of the original Amsterdam criteria,
and were subsequently revised by the National Cancer
Institute [3e5]. Predisposing germline mutations in the
DNA mismatch repair (MMR) genes, particularly MLH1
and MSH2, confirm the clinical diagnosis of HNPCC.
Mutations in MLH1 and MSH2 are spread in all regions,
without hot spots, which requires screening of entire genes.
Currently,therefore, sequencing is the key procedure in
diagnosing MMR defects.
Here we describe a previously unreported mutation in
the MSH2 gene and the molecular and clinical findings
within a family with two HNPCC-affected individuals.

2.1. Family history

* Corresponding author. Tel.: þ82-02-2228-2445; fax: þ82-02-3130956.
E-mail address: cjr0606@yuhs.ac (J.R. Choi).
0165-4608/08/$ e see front matterÓ 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.cancergencyto.2008.01.011

In a family with two affected members, the proband (45
years old at the time of diagnosis) received a low anterior
resection for a Duke B2, early-onset colorectal cancer
(Fig. 1). The tumor was mainly a mucinous carcinoma of
fungating type with central ulceration and extension into
the perirectal fattissue. The mother had been diagnosed
with adenocarcinoma of the transverse colon with pericolic
fat infiltration when she was 67 years old and underwent
right hemicolectomy (Duke D). Two siblings, a younger
brother and sister, had been diagnosed with colon polyp
but without other remarkable clinical findings. The proband’s father (who died at the age of 66) and another younger sister had no knownmedical conditions, including no
colon cancer, and no further study was assessed.
2.2. Preparation and analysis
Peripheral blood samples were obtained from the proband, mother, and younger brother with informed consent.
The extraction products were amplified using a GeneAmp
2700 thermocycler (Applied Biosystems, Foster City, CA)
for the entire MLH1 and MSH2 coding regions and splice

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