Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability

Jung Jin Kim, Myung Jin Baek, Lucia Kim, Nam Gyun Kim, Yongchan Lee, Si Young Song, Sung Hoon Noh, Hoguen Kim

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of gastric carcinomas, but the mutational profiles in precancerous lesions have not been characterized. To characterize the genetic events during gastric carcinogenesis, we analyzed DNA from 56 gastric adenomas and 167 gastric carcinomas for MSI using five microsatellite markers and for frameshift mutations at coding nucleotide repeats of the type II transforming growth factor β receptor, BAX, hMSH3, hMSH6, IGF II receptor, and E2F-4 genes. On the basis of the number of markers displaying instability per tumor, the tumors were divided into three groups: those with two or more of the five markers showing instability (high MSI [MSI-H]), those with one of the five markers showing instability (low MSI [MSI-L]), and those with no instability. MSI-H was found in 8 adenomas (14%) and 19 carcinomas (11%), and MSI-L was found in 8 adenomas (14%) and 9 carcinomas (5%). These groups were tested for correlations with several clinicopathologic parameters. MSI-H gastric adenomas were related to the high histologic grade of composing dysplastic glands (p = 0.004), and MSI-H gastric carcinomas were associated with exophytic tumor growth (p = 0.005). We found 48 frameshift mutations at coding nucleotide repeats of the six genes, and all mutations except one were found in MSI-H gastric tumors. Only one of the 17 MSI-L tumors showed frameshift mutations at coding nucleotide repeats of the transforming growth factor β receptor II gene. Compared with MSI-H gastric carcinomas, MSI-H adenomas had no mutations in the hMSH6 and the IGF II receptor genes, less frequent mutations in the transforming growth factor β receptor II (38% versus 63%), BAX (13% versus 37%), and hMSH3 (13% versus 37%) genes, and more frequent mutations in the E2F-4 (50% versus 37%) gene. Our findings suggest that MSI and E2F-4 mutations are early genetic events and that mutations of the other five genes are accumulated during the progression of gastric carcinomas with MSI.

Original languageEnglish
Pages (from-to)1113-1120
Number of pages8
JournalLaboratory Investigation
Volume79
Issue number9
Publication statusPublished - 1999 Sep 1

Fingerprint

Microsatellite Instability
Frameshift Mutation
Stomach
Nucleotides
Carcinoma
Adenoma
Mutation
Genes
Growth Factor Receptors
Transforming Growth Factors
IGF Type 2 Receptor
Neoplasms
Microsatellite Repeats

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Kim, Jung Jin ; Baek, Myung Jin ; Kim, Lucia ; Kim, Nam Gyun ; Lee, Yongchan ; Song, Si Young ; Noh, Sung Hoon ; Kim, Hoguen. / Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability. In: Laboratory Investigation. 1999 ; Vol. 79, No. 9. pp. 1113-1120.
@article{bb07c6340c1e4fc9ac910cea9f5e1a2d,
title = "Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability",
abstract = "Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of gastric carcinomas, but the mutational profiles in precancerous lesions have not been characterized. To characterize the genetic events during gastric carcinogenesis, we analyzed DNA from 56 gastric adenomas and 167 gastric carcinomas for MSI using five microsatellite markers and for frameshift mutations at coding nucleotide repeats of the type II transforming growth factor β receptor, BAX, hMSH3, hMSH6, IGF II receptor, and E2F-4 genes. On the basis of the number of markers displaying instability per tumor, the tumors were divided into three groups: those with two or more of the five markers showing instability (high MSI [MSI-H]), those with one of the five markers showing instability (low MSI [MSI-L]), and those with no instability. MSI-H was found in 8 adenomas (14{\%}) and 19 carcinomas (11{\%}), and MSI-L was found in 8 adenomas (14{\%}) and 9 carcinomas (5{\%}). These groups were tested for correlations with several clinicopathologic parameters. MSI-H gastric adenomas were related to the high histologic grade of composing dysplastic glands (p = 0.004), and MSI-H gastric carcinomas were associated with exophytic tumor growth (p = 0.005). We found 48 frameshift mutations at coding nucleotide repeats of the six genes, and all mutations except one were found in MSI-H gastric tumors. Only one of the 17 MSI-L tumors showed frameshift mutations at coding nucleotide repeats of the transforming growth factor β receptor II gene. Compared with MSI-H gastric carcinomas, MSI-H adenomas had no mutations in the hMSH6 and the IGF II receptor genes, less frequent mutations in the transforming growth factor β receptor II (38{\%} versus 63{\%}), BAX (13{\%} versus 37{\%}), and hMSH3 (13{\%} versus 37{\%}) genes, and more frequent mutations in the E2F-4 (50{\%} versus 37{\%}) gene. Our findings suggest that MSI and E2F-4 mutations are early genetic events and that mutations of the other five genes are accumulated during the progression of gastric carcinomas with MSI.",
author = "Kim, {Jung Jin} and Baek, {Myung Jin} and Lucia Kim and Kim, {Nam Gyun} and Yongchan Lee and Song, {Si Young} and Noh, {Sung Hoon} and Hoguen Kim",
year = "1999",
month = "9",
day = "1",
language = "English",
volume = "79",
pages = "1113--1120",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "9",

}

Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability. / Kim, Jung Jin; Baek, Myung Jin; Kim, Lucia; Kim, Nam Gyun; Lee, Yongchan; Song, Si Young; Noh, Sung Hoon; Kim, Hoguen.

In: Laboratory Investigation, Vol. 79, No. 9, 01.09.1999, p. 1113-1120.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability

AU - Kim, Jung Jin

AU - Baek, Myung Jin

AU - Kim, Lucia

AU - Kim, Nam Gyun

AU - Lee, Yongchan

AU - Song, Si Young

AU - Noh, Sung Hoon

AU - Kim, Hoguen

PY - 1999/9/1

Y1 - 1999/9/1

N2 - Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of gastric carcinomas, but the mutational profiles in precancerous lesions have not been characterized. To characterize the genetic events during gastric carcinogenesis, we analyzed DNA from 56 gastric adenomas and 167 gastric carcinomas for MSI using five microsatellite markers and for frameshift mutations at coding nucleotide repeats of the type II transforming growth factor β receptor, BAX, hMSH3, hMSH6, IGF II receptor, and E2F-4 genes. On the basis of the number of markers displaying instability per tumor, the tumors were divided into three groups: those with two or more of the five markers showing instability (high MSI [MSI-H]), those with one of the five markers showing instability (low MSI [MSI-L]), and those with no instability. MSI-H was found in 8 adenomas (14%) and 19 carcinomas (11%), and MSI-L was found in 8 adenomas (14%) and 9 carcinomas (5%). These groups were tested for correlations with several clinicopathologic parameters. MSI-H gastric adenomas were related to the high histologic grade of composing dysplastic glands (p = 0.004), and MSI-H gastric carcinomas were associated with exophytic tumor growth (p = 0.005). We found 48 frameshift mutations at coding nucleotide repeats of the six genes, and all mutations except one were found in MSI-H gastric tumors. Only one of the 17 MSI-L tumors showed frameshift mutations at coding nucleotide repeats of the transforming growth factor β receptor II gene. Compared with MSI-H gastric carcinomas, MSI-H adenomas had no mutations in the hMSH6 and the IGF II receptor genes, less frequent mutations in the transforming growth factor β receptor II (38% versus 63%), BAX (13% versus 37%), and hMSH3 (13% versus 37%) genes, and more frequent mutations in the E2F-4 (50% versus 37%) gene. Our findings suggest that MSI and E2F-4 mutations are early genetic events and that mutations of the other five genes are accumulated during the progression of gastric carcinomas with MSI.

AB - Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of gastric carcinomas, but the mutational profiles in precancerous lesions have not been characterized. To characterize the genetic events during gastric carcinogenesis, we analyzed DNA from 56 gastric adenomas and 167 gastric carcinomas for MSI using five microsatellite markers and for frameshift mutations at coding nucleotide repeats of the type II transforming growth factor β receptor, BAX, hMSH3, hMSH6, IGF II receptor, and E2F-4 genes. On the basis of the number of markers displaying instability per tumor, the tumors were divided into three groups: those with two or more of the five markers showing instability (high MSI [MSI-H]), those with one of the five markers showing instability (low MSI [MSI-L]), and those with no instability. MSI-H was found in 8 adenomas (14%) and 19 carcinomas (11%), and MSI-L was found in 8 adenomas (14%) and 9 carcinomas (5%). These groups were tested for correlations with several clinicopathologic parameters. MSI-H gastric adenomas were related to the high histologic grade of composing dysplastic glands (p = 0.004), and MSI-H gastric carcinomas were associated with exophytic tumor growth (p = 0.005). We found 48 frameshift mutations at coding nucleotide repeats of the six genes, and all mutations except one were found in MSI-H gastric tumors. Only one of the 17 MSI-L tumors showed frameshift mutations at coding nucleotide repeats of the transforming growth factor β receptor II gene. Compared with MSI-H gastric carcinomas, MSI-H adenomas had no mutations in the hMSH6 and the IGF II receptor genes, less frequent mutations in the transforming growth factor β receptor II (38% versus 63%), BAX (13% versus 37%), and hMSH3 (13% versus 37%) genes, and more frequent mutations in the E2F-4 (50% versus 37%) gene. Our findings suggest that MSI and E2F-4 mutations are early genetic events and that mutations of the other five genes are accumulated during the progression of gastric carcinomas with MSI.

UR - http://www.scopus.com/inward/record.url?scp=0005509268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0005509268&partnerID=8YFLogxK

M3 - Article

VL - 79

SP - 1113

EP - 1120

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 9

ER -