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Journal of Ovarian Research

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Open Access 01-12-2017 | Brief Communication

PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor

Authors: Wen-Chung Wang, Ya-Ting Lee, Yen-Chein Lai

Published in: Journal of Ovarian Research | Issue 1/2017

Abstract

Background

Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C > G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor.

Findings

In this study, the DNA sequences of four genes, MSH2, MLH1, MSH6, and PMS2, in the DNA mismatch repair system were determined via direct sequencing to elucidate the exact mechanism for the development of this granulosa cell tumor. The results showed that two missense germline mutations, T485K and N775L, inactivate the PMS2 gene.

Conclusions

The results of this case study indicated that although FOXL2 402C > G mutation determines the development of granulosa cell tumor, PMS2 mutation may be the initial driver of carcinogenesis. Immunohistochemistry-based tumor testing for mismatch repair gene expression may be necessary for granulosa cell tumors to determine their malignant potential or if they are part of Lynch syndrome.

Scully RE. Classification of human ovarian tumors. Environ Health Perspect. 1987;73:15–25.CrossRefPubMedPubMedCentral

Outwater EK, Wagner BJ, Mannion C, McLarney JK, Kim B. Sex cord-stromal and steroid cell tumors of the ovary. Radiographics. 1998;18:1523–46.CrossRefPubMed

Schumer ST, Cannistra SA. Granulosa cell tumor of the ovary. J Clin Oncol. 2003;21:1180–9.CrossRefPubMed

Geetha P, Nair MK. Granulosa cell tumours of the ovary. Aust N Z J Obstet Gynaecol. 2010;50:216–20.CrossRefPubMed

Mancari R, Portuesi R, Colombo N. Adult granulosa cell tumours of the ovary. Curr Opin Oncol. 2014;26:536–41.CrossRefPubMed

Jamieson S, Fuller PJ. Molecular pathogenesis of granulosa cell tumors of the ovary. Endocr Rev. 2012;33:109–44.CrossRefPubMed

Kavuri S, Kulkarni R, Reid-Nicholson M. Granulosa cell tumor of the ovary: cytologic findings. Acta Cytol. 2010;54:551–9.PubMed

Shah SP, Kobel M, Senz J, Morin RD, Clarke BA, Wiegand KC, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med. 2009;360:2719–29.CrossRefPubMed

Wang WC, Lai YC. Molecular pathogenesis in granulosa cell tumor is not only due to somatic FOXL2 mutation. J Ovarian Res. 2014;7:88.PubMedPubMedCentral

10.

Georges A, Auguste A, Bessiere L, Vanet A, Todeschini AL, Veitia RA. FOXL2: a central transcription factor of the ovary. J Mol Endocrinol. 2014;52:R17–33.CrossRefPubMed

11.

Nakamura K, Banno K, Yanokura M, Iida M, Adachi M, Masuda K, et al. Features of ovarian cancer in Lynch syndrome (review). Mol Clin Oncol. 2014;2:909–16.PubMedPubMedCentral

12.

Nakagawa H, Lockman JC, Frankel WL, Hampel H, Steenblock K, Burgart LJ, et al. Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res. 2004;64:4721–7.CrossRefPubMed

13.

Balog CI, Stavenhagen K, Fung WL, Koeleman CA, McDonnell LA, Verhoeven A, et al. N-glycosylation of colorectal cancer tissues: a liquid chromatography and mass spectrometry-based investigation. Mol Cell Proteomics. 2012;11:571–85.CrossRefPubMedPubMedCentral

14.

Wang Q, Lasset C, Desseigne F, Saurin JC, Maugard C, Navarro C, et al. Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer. Hum Genet. 1999;105:79–85.PubMed

15.

Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81:214–8.CrossRefPubMed

16.

Morohashi K. The ontogenesis of the steroidogenic tissues. Genes Cells. 1997;2:95–106.CrossRefPubMed

17.

Raymond VM, Everett JN, Furtado LV, Gustafson SL, Jungbluth CR, Gruber SB, et al. Adrenocortical carcinoma is a lynch syndrome-associated cancer. J Clin Oncol. 2013;31:3012–8.CrossRefPubMedPubMedCentral

18.

Committee on Practice Bulletins-Gynecology; Society of Gynecologic Oncology. ACOG practice bulletin No. 147: Lynch syndrome. Obstet Gynecol. 2014;124:1042–54.CrossRef

Title: PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor
Authors: Wen-Chung Wang
Ya-Ting Lee
Yen-Chein Lai
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-017-0317-4

At a glance: The STEP trials

Springer Medicine

PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor

Abstract

Background

Findings

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Findings

Conclusions

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