Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer

Shilpa, .; Bhagat, Rahul; Premalata, C S; Pallavi, V. R.; Krishnamoorthy, Lakshmi

doi:10.1016/j.ygeno.2014.08.016

Cited by 25 publications

(23 citation statements)

References 32 publications

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“…The extra band originated from one of two alleles with the characteristic stutter at one or more repeat unit below the main signal and the new allele differed from the assigned ancestral allele by one repeat. Microsatellite instability (MSI) was reported in leukemia [25], gastric [26], ovarian [27], breast [28], and colon cancers [29]. A total of 32 cell lines with MSI were identified with three banding patterns, including 7 liver cancer cell lines, 8 cervical cancer cell lines, 2 ovarian cancer cell lines, 1 leukemia cell line, 3 stomach cancer cell lines, 4 breast cancer cell lines, 1 colon cancer cell line, 2 osteosarcoma cancer cell lines, 1 pancreatic cancer cell line, 1 kidney cell line, 1 lung cancer cell line and 1 lymph cancer cell line.…”

Section: Resultsmentioning

confidence: 99%

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

et al. 2017

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In recent years, biological research involving human cell lines has been rapidly developing in China. However, some of the cell lines are not authenticated before use. Therefore, misidentified and/or cross-contaminated cell lines are unfortunately commonplace. In this study, we present a comprehensive investigation of cross-contamination and misidentification for a panel of 278 cell lines from 28 institutes in China by using short tandem repeat profiling method. By comparing the DNA profiles with the cell bank databases of ATCC and DSMZ, a total of 46.0% (128/278) cases with cross-contamination/misidentification were uncovered coming from 22 institutes. Notably, 73.2% (52 out of 71) of the cell lines established by the Chinese researchers were misidentified and accounted for 40.6% of total misidentification (52/128). Further, 67.3% (35/52) of the misidentified cell lines established in laboratories of China were HeLa cells or a possible hybrid of HeLa with another kind of cell line. Furthermore, the bile duct cancer cell line HCCC-9810 and degenerative lung cancer Calu-6 exhibited 88.9% match in the ATCC database (9-loci), indicating that they were from the same origin. However, when we used 21-loci to compare these two cell lines with the same algorithm, the percent match was only 48.2%, indicating that these two cell lines were different. The SNP profiles of HCCC-9810 and Calu-6 also revealed that they were different cell lines. 150 cell lines with unique profiles demonstrated a wide range of in vitro phenotypes. This panel of 150 genomically validated cancer cell lines represents a valuable resource for the cancer research community and will advance our understanding of the disease by providing a standard reference for cell lines that can be used for biological as well as preclinical studies.

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Section: Resultsmentioning

confidence: 99%

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

et al. 2017

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“…In epithelial ovarian cancer, microsatellite instability (MSI) was observed in 14.9% of cases in a series of 834 samples [ 38 ]. MSI can be due to germline mutation within at least one of four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ), but more likely to hypermethylation of the MLH1 promoter in sporadic cancers, including ovarian cancers, with an occurrence of 37.5% [ 39 ]. With the exception of germ cell tumors, hypermethylation of MLH1 was observed in more than half of our series of ovarian epithelial tumors.…”

Section: Discussionmentioning

confidence: 99%

Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers

Losi

Fonda

Saponaro

et al. 2018

IJMS

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Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes (BRCA1, MGMT, and MLH1), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of MGMT, OSMR, ESR1, and FOXL2 and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.

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“…It is unclear whether MSI is a reliable proxy for loss of MMR in ovarian cancer. Some studies have identified MSI-H in more than 60% of ovarian epithelial tumors, while MMR protein expression was intact in a subset of these cases [ 30 ], and MSI is also found in more than 50% of normal ovarian tissues [ 30 31 ]. Other studies have found a lower MSI-H frequency of 10%–20% [ 27 32 ].…”

Section: Discussionmentioning

confidence: 99%

Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

et al. 2018

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ObjectiveLynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history.MethodsThe subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed.ResultsOf the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation.ConclusionThis is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

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Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer

Cited by 25 publications

References 32 publications

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

Investigation of Cross-Contamination and Misidentification of 278 Widely Used Tumor Cell Lines

Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers

Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

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