Mutation Profiles Detected by New Generation DNA Sequence Analysis in Gynecological Cancers: Single Centre Case Series Results

Abstract

Our objective is to investigate the mutation frequency and sequences of our patients, who underwent surgery with a diagnosis of ovarian (OC) and endometrial cancer (EC) and subsequently underwent genetic mutation analysis, regardless of age and family history. In recent years, apart from the development of preventive strategies, opportunities in treatment options and increase in genetic studies have increased the interest in hereditary cancers. The most common hereditary gynecological cancers are hereditary breast ovarian cancer (HBOC) and Lynch Syndrome (LS). The low prevalence of the disease, cost of testing, and ethical reasons make population-based screening impractical. 37 patients diagnosed with endometrial cancer and 15 patients diagnosed with ovarian cancer were included in the study, and their genetic research was conducted in our department between 01.04.2018 and 01.10.2019. A large familial panel test consisting of 25 genes including BRCA1/2 and LS genes (MLH1, MSH2, MSH6, PMS 2) was performed. Pathological mutation was found in 1 MLH1 and 1 ATM genes in 27 patients with endometrial cancer who underwent familial gene panel test (3.7% LS, 3.7% non LS). Eleven patients had a variant mutation of uncertain significance (VUS) (40.7%). No pathological mutation was found in our 20 patients with endometrial cancer who were investigated for BRCA mutation. In our 14 patients with ovarian cancer whose BRCA mutation was investigated, 3 pathological variants were identified, and all of them were in BRCA1 gene (HBOC 21.4%). Pathological mutations in 1 MSH6 and 1 ATM genes were observed in 4 patients with ovarian cancer whose familial cancer panel was evaluated. The proliferation of comprehensive familial mutation data in ovarian and endometrial cancers and their sharing in the literature will reduce VUS rates, reveal the role of genes other than BRCA and LS in gynecological cancers, and create new screening algorithms.

Keywords

• Gynecologic cancers
• Hereditary
• Genetic counseling

Jinekolojik Kanserlerde Yeni Nesil DNA Dizi Analizi ile Saptanan Mutasyon Profilleri: Tek Merkez Vaka Serisi Sonuçlarımız

Abstract

Amacımız, yaş ve aile hikayesinden bağımsız olarak merkezimizde over (OC) ve endometriyum kanseri (EC) tanısı ile cerrahisi ve ardından genetik mutasyon analizi uygulanan hastalarımızın mutasyon sıklığını ve sekanslarını araştırmaktır. Son yıllarda önleyici stratejilerin gelişimi dışında tedavi seçeneklerindeki fırsatlar ve genetik çalışmaların artışı herediter kanserlere ilgiyi arttırmıştır. En sık görülen herediter jinekolojik kanserler; herediter meme over kanseri (HBOC) ve Lynch Sendromu (LS) dur. Hastalığın düşük prevalansı, test pahalılığı ve etik sebepler popülasyon bazlı taramayı kullanışsız hale getirmektedir. Birimimizde 01.04.2018-01.10.2019 tarihleri arasında genetik araştırması yapılan 37 EC ve 15 OC tanısı almış hastamız çalışmaya dahil edilmiştir. BRCA1/2 ve LS genlerini de içeren (MLH1, MSH2, MSH6, PMS 2) 25 genden oluşan geniş ailevi panel testi uygulanmıştır. Ailevi gen paneli testi yapılan 27 EC hastamızda, 1 MLH1 ve 1 ATM geninde patolojik mutasyon saptandı (%3.7 LS,%3.7 non LS). 11 hastada önemi belirsiz varyant mutasyon (VUS) görüldü (%40.7). BRCA mutasyon araştırması yapılan 20 EC’li hastamızda patolojik mutasyon saptanmadı. BRCA mutasyonu araştırılan 14 OC’lu hastamızda 3 patolojik varyant identifiye edildi ve hepsi BRCA1 genindeydi (HBOC %21,4). Ailevi kanser paneli değerlendirilen 4 OC’lu hastada 1 MSH6 ve 1 ATM geninde patolojik mutasyonlar izlendi. Over ve endometriyum kanserlerinde ailevi geniş mutasyon verilerinin çoğalması ve literatürde paylaşımı VUS oranlarını azaltacak, BRCA ve LS dışındaki genlerin jinekolojik kanserlerdeki rolünü ortaya çıkartacak ve yeni tarama algoritmalarını oluşturacaktır.

Keywords

• Jinekolojik kanserler
• Heredite
• Genetik analiz

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