MLH3 mutation in endometrial cancer

Nicholas P. Taylor, Matthew A. Powell, Randall K. Gibb, Janet S. Rader, Phyllis C. Huettner, Stephen N Thibodeau, David G. Mutch, Paul J. Goodfellow

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

MLH3 is a recently described member of the DNA mismatch repair gene family. Based on its interaction with the MutL homologue MLH1, it was postulated that MLH3 might play a role in tumorigenesis. Germ line and somatic mutations in MLH3 have been identified in a small fraction of colorectal cancers, but the role of MLH3 in colorectal cancer tumorigenesis remains controversial. We investigated MLH3's role in endometrial tumorigenesis through analysis of tumor and germ line DNA from 57 endometrial cancer patients who were at increased risk for having inherited cancer susceptibility. Patients with known MSH2 or MSH6 mutations were excluded as well as those who had MLH1-methylated tumors. Sixteen different variants were identified by single-strand conformational variant analysis. Of the 12 missense changes identified, three were somatic mutations. One patient had a germ line missense variant and loss of heterozygosity (LOH) in her tumor specimen. There was no evidence of MLH3 promoter methylation based on combined bisulfite restriction analysis. The identification of inherited missense variants, somatic missense mutations (present in 3 of 57 tumors), and LOH in the tumor from a patient with a germ fine missense change suggest a role for MLH3 in endometrial tumorigenesis.

Original languageEnglish (US)
Pages (from-to)7502-7508
Number of pages7
JournalCancer Research
Volume66
Issue number15
DOIs
StatePublished - Aug 1 2006

Fingerprint

Endometrial Neoplasms
Mutation
Carcinogenesis
Neoplasms
Loss of Heterozygosity
Germ Cells
Colorectal Neoplasms
DNA Mismatch Repair
Germ-Line Mutation
Missense Mutation
Methylation
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Taylor, N. P., Powell, M. A., Gibb, R. K., Rader, J. S., Huettner, P. C., Thibodeau, S. N., ... Goodfellow, P. J. (2006). MLH3 mutation in endometrial cancer. Cancer Research, 66(15), 7502-7508. https://doi.org/10.1158/0008-5472.CAN-06-0248

MLH3 mutation in endometrial cancer. / Taylor, Nicholas P.; Powell, Matthew A.; Gibb, Randall K.; Rader, Janet S.; Huettner, Phyllis C.; Thibodeau, Stephen N; Mutch, David G.; Goodfellow, Paul J.

In: Cancer Research, Vol. 66, No. 15, 01.08.2006, p. 7502-7508.

Research output: Contribution to journalArticle

Taylor, NP, Powell, MA, Gibb, RK, Rader, JS, Huettner, PC, Thibodeau, SN, Mutch, DG & Goodfellow, PJ 2006, 'MLH3 mutation in endometrial cancer', Cancer Research, vol. 66, no. 15, pp. 7502-7508. https://doi.org/10.1158/0008-5472.CAN-06-0248
Taylor NP, Powell MA, Gibb RK, Rader JS, Huettner PC, Thibodeau SN et al. MLH3 mutation in endometrial cancer. Cancer Research. 2006 Aug 1;66(15):7502-7508. https://doi.org/10.1158/0008-5472.CAN-06-0248
Taylor, Nicholas P. ; Powell, Matthew A. ; Gibb, Randall K. ; Rader, Janet S. ; Huettner, Phyllis C. ; Thibodeau, Stephen N ; Mutch, David G. ; Goodfellow, Paul J. / MLH3 mutation in endometrial cancer. In: Cancer Research. 2006 ; Vol. 66, No. 15. pp. 7502-7508.
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