Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

Özdemir, Taha Reşi̇d; Alan, Murat; Şancı, Muzaffer; Koç, Altuğ

doi:10.4274/balkanmedj.2018.0922

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Our study reports a higher mutation rate in the MMR genes (42.1%), compared to other studies (18–22.7%) [ 16 , 20 ]. Particularly, in our cohort of patients, we found no differences in the percentage of pathogenic variants in the analyzed genes, as we revealed a percentage of 50% in both MLH1 and MSH2 .…”

Section: Discussioncontrasting

confidence: 70%

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Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer

et al. 2021

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Endometrial cancer (EC) is the fifth most common cancer in women from developed countries, accounting for 4.8% of new cases and 2.1% of deaths. The genetic basis for the familial risk of endometrial cancer has not been completely defined. Mostly, hereditary EC is part of two syndromes as Lynch syndrome (LS) and Hereditary Breast and Ovarian Cancer syndrome (HBOC). LS is the prototypical hereditary cancer syndrome in EC and accounts for 2–6% of all endometrial cancers. This disease is caused by autosomal dominant mutations in DNA mismatch repair (MMR) genes. Patients carrying a germline mutation in one of the MMR genes have a cumulative lifetime risk to develop EC of 20–70%. HBOC is an autosomal dominantly inherited disease, which mostly predisposes to breast and ovarian cancers, but it can be also associated with other malignancies. HBOC results from germline mutations in BRCA1/2 genes. The aim of this study was to determine the mutational status of a cohort of 40 EC patients, 19 belonging to families with LS and 21 to HBOC. Mutation analysis of MLH1, MSH2, BRCA1 and BRCA2 genes showed pathogenic variants in 17/40 (42.5%) patients. Out of 19 patients belonging to LS families, 8 (42.1%) showed a pathogenic variant. Out of 21 patients belonging to HBOC families, 9 (42.8%) showed a pathogenic variant. 1/21 (4.8%) patient report 1 variant of unknown significance (UV), c.599 C > T (p.T200I), in BRCA2. Moreover, in 1/21 (4.8%) patient we identified a novel missense variant in BRCA2, c.9541A > T (p.Met3181Leu). Mutational analysis was extended to family members, both healthy and cancer affected, of mutated patients; all the tested relatives affected with cancer displayed the pathogenic variant. Our data suggest that patients with hereditary EC have a high percentage of mutations in the LS and HBOC main susceptibility genes; therefore, the surveillance for EC, already indicated in LS patients, should also be recommended for patients with HBOC.

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Section: Discussioncontrasting

confidence: 70%

“…Mutational analysis of exons of MLH1 , MSH2 , BRCA1 , BRCA2 and adjacent intronic regions was performed with NGS, as previously described [ 15 , 16 ]. The presence of the pathogenic variant was confirmed on the other blood sample by Sanger sequencing, as previously described [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer

et al. 2021

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“…The APC gene has been proposed as a prominent tumor-promoting gene participating in the tumorigenesis of CRC and/or adenomatous polyposis coli. 33 APC pathogenic/likely pathogenic variations were present in 3 cases (3.75%) of colon cancer and familial adenomatous polyposis coli in the present study. Liu and Tan 8 analyzed a 183-gene panel in gastrointestinal cancers and reported that the 7 most frequently mutated genes were MSH2, ATM, FANCD2, ATR, BRCA2, FANCA , and BRCA1.…”

Section: Discussionsupporting

confidence: 53%

Targeted next-generation sequencing as a diagnostic tool in gastrointestinal system cancer/polyposis patients

Yalçıntepe

Gürkan

Demır

et al. 2020

Tumori

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Background: Recent advances in next-generation sequencing (NGS) technology have enabled multigene testing and changed the diagnostic approach to hereditary gastrointestinal cancer/polyposis syndromes. The aim of this study was to analyze different cancer predisposition genes in hereditary/sporadic gastrointestinal cancer/polyposis. Methods: Cancer predisposition genes were analyzed with an Illumina MiSeq NGS system in 80 patients with gastrointestinal cancer/polyposis who were examined between the years 2016 and 2019. Deletion/duplication analysis of MLH1, MSH2, and EPCAM genes was performed by using the multiplex ligation-dependent probe amplification method. Results: Germline testing of hereditary cancer-related genes was performed in 80 patients with gastrointestinal cancer/polyposis. A total of 30 variants in 30 cases (37.5%) were assessed as pathogenic/likely pathogenic. A total of 19 heterozygous variants were assessed as variants of uncertain clinical significance in 17 cases (21.25%) and 18 (22.5%) novel variations (9 pathogenic/likely pathogenic, 9 variants of uncertain significance) were determined. In 4 (5%) cases, multiplex ligation-dependent probe amplification detected deletions in MLH1, MSH2, and EPCAM genes. Conclusion: The accumulation of analyses with multigene testing will increase the available data for cancer predisposition genes in hereditary gastrointestinal cancer/polyposis. Educational campaigns for prevention, efficient screening programs, and more personalized care based on the profile of individual patients are necessary.

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“…Endometrial carcinoma is divided into four different molecular subtypes: POLE acculturated; Microsatellite instability hypermutated (MSI-H); Copy number abnormalities-low (CN-L), and Copy number abnormalities-high (CN-H). Literature has reported that MSI exists in many types of solid tumors, such as EC, colorectal cancer, and lung cancer [ 22 ], and is also related to Lynch and sporadic endometrial carcinoma [ 23 ]. In TCGA studies, MSI high mutants accounted for about 30% of EC, 28.6% of low-grade EEC and 54.3% of high-grade EEC belonged to MSI type.…”

Section: Discussionmentioning

confidence: 99%

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report

Yang

et al. 2022

BMC Women's Health

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Background Endometrial carcinoma (EC) is a common malignant tumor of the female reproductive system, often accompanied by lymph node metastasis. Artificial vascular implantation is a common surgical treatment for mediastinal tumors and abdominal aortic aneurysms but is rarely used in gynecological surgery. Case presentation A 54-year-old female patient was first admitted to the hospital in January 2018 due to “irregular vaginal bleeding over 3 months”. CT showed a mass in the uterine cavity, and several swollen lymph nodes in the retroperitoneum and pelvic cavity. The initial diagnosis was an endometrial malignant tumor. We performed radical endometrial cancer surgery with parallel resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, bilateral external iliac arteries, and artificial vessel replacement, which was successful, with good postoperative recovery and no lesion progression at 3 years postoperative follow-up. Conclusion This is an early case of gynecological clinical use of prostheses. Through multidisciplinary cooperation, the surgical resection rate of patients with EC in radical surgery was improved without serious fatal complications and achieved a high long-term postoperative survival rate.

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Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

Cited by 4 publications

References 25 publications

Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer

Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer

Targeted next-generation sequencing as a diagnostic tool in gastrointestinal system cancer/polyposis patients

Resection of inferior vena cava, abdominal aorta, bilateral common iliac arteries, and bilateral partial external iliac arteries with artificial vessel replacement during radical endometrial cancer surgery: a case report

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