Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability

Peter C. Lim, David Tester, William Arthur Cliby, Steven C. Ziesmer, Patrick C. Roche, Lynn Hartmann, Stephen N Thibodeau, Karl C. Podratz, Robert Brian Jenkins

Research output: Contribution to journalArticle

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Abstract

DNA mismatch repair genes have been reported to play a role in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). Mutations of DNA mismatch repair genes have accounted for 90% of HNPCC-related colon and endometrial tumors. These mutations have been associated with microsatellite instability (MIN). Because endometrial cancer (EC) is the most common extracolonic malignancy associated with HNPCC, we hypothesized that similar molecular alterations may occur in sporadic endometrial tumors exhibiting MIN. Mutational analysis of the MSH2 and MLH1 genes was undertaken in sporadic EC that demonstrate MIN to determine the role of these genes in the pathogenesis of sporadic ECs. Established microsatellite markers were used to determine the incidence of MIN from 28 patients with sporadic EC. MIN was observed in 32% (9 of 28) of the tumor specimens analyzed. Mutational analysis of MSH2 and MLH1 genes was performed by immunohistochemical analysis and direct sequencing of tumor specimens that exhibited MIN. All 28 tumor specimens exhibited strong nuclear staining with both MSH2 and MLH1 antibodies, suggesting the absence of mutations. Sequencing of all exons of both the MSH2 and MLH1 genes in the nine MIN-positive tumor specimens demonstrated no mutations. We conclude that the MSH2 and MLH1 genes do not play a role in the pathogenesis of sporadic endometrial cancer.

Original languageEnglish (US)
Pages (from-to)1907-1911
Number of pages5
JournalClinical Cancer Research
Volume2
Issue number11
StatePublished - Nov 1996

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Microsatellite Instability
DNA Mismatch Repair
Mutation
Endometrial Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Genes
Neoplasms
Microsatellite Repeats
Colonic Neoplasms
Exons
Staining and Labeling
Antibodies
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability. / Lim, Peter C.; Tester, David; Cliby, William Arthur; Ziesmer, Steven C.; Roche, Patrick C.; Hartmann, Lynn; Thibodeau, Stephen N; Podratz, Karl C.; Jenkins, Robert Brian.

In: Clinical Cancer Research, Vol. 2, No. 11, 11.1996, p. 1907-1911.

Research output: Contribution to journalArticle

Lim, Peter C. ; Tester, David ; Cliby, William Arthur ; Ziesmer, Steven C. ; Roche, Patrick C. ; Hartmann, Lynn ; Thibodeau, Stephen N ; Podratz, Karl C. ; Jenkins, Robert Brian. / Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 11. pp. 1907-1911.
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abstract = "DNA mismatch repair genes have been reported to play a role in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). Mutations of DNA mismatch repair genes have accounted for 90{\%} of HNPCC-related colon and endometrial tumors. These mutations have been associated with microsatellite instability (MIN). Because endometrial cancer (EC) is the most common extracolonic malignancy associated with HNPCC, we hypothesized that similar molecular alterations may occur in sporadic endometrial tumors exhibiting MIN. Mutational analysis of the MSH2 and MLH1 genes was undertaken in sporadic EC that demonstrate MIN to determine the role of these genes in the pathogenesis of sporadic ECs. Established microsatellite markers were used to determine the incidence of MIN from 28 patients with sporadic EC. MIN was observed in 32{\%} (9 of 28) of the tumor specimens analyzed. Mutational analysis of MSH2 and MLH1 genes was performed by immunohistochemical analysis and direct sequencing of tumor specimens that exhibited MIN. All 28 tumor specimens exhibited strong nuclear staining with both MSH2 and MLH1 antibodies, suggesting the absence of mutations. Sequencing of all exons of both the MSH2 and MLH1 genes in the nine MIN-positive tumor specimens demonstrated no mutations. We conclude that the MSH2 and MLH1 genes do not play a role in the pathogenesis of sporadic endometrial cancer.",
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AB - DNA mismatch repair genes have been reported to play a role in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). Mutations of DNA mismatch repair genes have accounted for 90% of HNPCC-related colon and endometrial tumors. These mutations have been associated with microsatellite instability (MIN). Because endometrial cancer (EC) is the most common extracolonic malignancy associated with HNPCC, we hypothesized that similar molecular alterations may occur in sporadic endometrial tumors exhibiting MIN. Mutational analysis of the MSH2 and MLH1 genes was undertaken in sporadic EC that demonstrate MIN to determine the role of these genes in the pathogenesis of sporadic ECs. Established microsatellite markers were used to determine the incidence of MIN from 28 patients with sporadic EC. MIN was observed in 32% (9 of 28) of the tumor specimens analyzed. Mutational analysis of MSH2 and MLH1 genes was performed by immunohistochemical analysis and direct sequencing of tumor specimens that exhibited MIN. All 28 tumor specimens exhibited strong nuclear staining with both MSH2 and MLH1 antibodies, suggesting the absence of mutations. Sequencing of all exons of both the MSH2 and MLH1 genes in the nine MIN-positive tumor specimens demonstrated no mutations. We conclude that the MSH2 and MLH1 genes do not play a role in the pathogenesis of sporadic endometrial cancer.

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