Şenol ÇİTLİ, Yelda DAĞCIOĞLU, Esra AYDIN, Kemal KURTÇU

KARADENİZ BÖLGESİNDEKİ MEME VE YUMURTALIK KANSERİ HASTALARINDA GERMLİNE KANSER YATKINLIK GENLERİNİN MUTASYON SPEKTRUMU: TEK MERKEZ DENEYİMİ

Giriş: Meme kanseri kadınlarda en sık görülen kanserdir ve kansere bağlı ölümlerin en sık nedenlerinden biridir. Over kanseri, jinekolojik kanserler arasında ikinci en sık kanser türüdür ve bu hastaların çoğu geç tanı aldığından dolayı mortalitesi en yüksek jinekolojik kanser olarak bilinir. Bu çalışmada ülkemiz karadeniz bölgesinde Meme ve Over kanseri tanısı almış yüksek risk grubundaki hastalarda BRCA1 ve BRCA2 başta olmak üzere sorumlu olabilecek onkogen mutasyonlarının prevalansı ve bölge populasyonumuza özgü varyantları belirlemeyi amaçladık. Materyal ve metod: Çalışmada Ağustos 2017–0cak 2022 aralığında merkezimize başvuran ve genetik test kriterlerini karşılayan 223 hasta analiz edilmiştir. Çalışmaya alınan hastalarda onkogenetik panel (34 gen) kapsamındaki genlerde germ-line zararlı varyantları tanımlamak için (Next generation sequencing (NGS)) yeni nesil dizileme kullanıldı. Bulgular: Çalışma kapsamında analiz edilen 195 Meme kanserli ve 28 Over kanserli olmak üzere toplam 223 hastanın BRCA1 (%4,9) ve BRCA2 (6,7) genlerinde toplam 26 (%11,6) hastada 15 farklı Patojenik varyant saptanmıştır. BRCA1 ve BRCA2 genleri dışındaki diğer 32 onkogenin analizinde ise toplam 35 hastada (%15,7) 26 farklı Patojenik (P) veya Likely Patojenik (LP) varyant tespit edilmiştir. Analiz edilen 223 meme/over kanserli hasta beraber düşünüldüğünde ise 61 hastada (%27.3) 41 farklı Patojenik (P) veya Likely Patojenik (LP) variant tespit edilmiştir. Bunlara ek olarak Çalışmaki 73 hastada (%32.7) ise 65 farklı VUS (Variant of Uncertain Significance = Önemi Belirsiz Varyant) saptanmıştır. Sonuç: Çalışma karadeniz bölgesindeki üçüncü basamak bir hastanede yürütülmüş olup bildiğimiz kadarıyla BRCA genleri dışındaki kanser genleri açısından bölgemize dair ilk verileri ortaya koymaktadır. Kalıtsal meme/over kanseri genetik yatkınlık spektrumunun daha fazla anlaşılması için BRCA1 ve BRCA2 genlerinin yanı sıra diğer meme/over ca açısından yüksek risk taşıyan BRCA1 ve BRCA2 genleri dışındaki kanser genlerine özgü risklerin de aydınlatılması gerekmektedir. Bundan dolayı risk grubundaki hastalara rutin BRCA1 ve BRCA2 genlerine ek olarak çoklu gen panel testine ihtiyaç vardır. Çalışmada BRCA2 geninde 2 novel variant saptanırken BRCA genleri dışındaki onkogenlerde 5 novel variant tespit edildi. Ek olarak çalışmamız sonucunda ülkemize spesifik varyant havuzuna da katkı sağlandı.

Anahtar Kelimeler:

ngs, brca1, chek2, Meme/Over kanseri

SPECTRUM OF GERMLINE CANCER SUSCEPTIBILITY GENE MUTATIONS IN BREAST AND OVARIAN CANCER PATIENTS IN THE BLACK SEA REGION OF TURKEY: SINGLE CENTER EXPERIENCE

Introduction: Breast cancer consists huge amount of the cancerrelated death in population. Ovarian cancer is the second most frequent seen type of gynecological cancer and has the highest mortality among gynecological cancers since most cases are detected late. The current study intended to determine the prevalence of oncogene mutations, especially BRCA1 and BRCA2, in high-risk patients diagnosed with ovarian and breast cancer in the Black Sea region of our country. Material and method: Between August 2017 and January 2022, a total of 223 individuals who applied to our center and met the genetic test criteria were included in the study. Next-generation sequencing (NGS) was used to detect germ-line deleterious variants in genes included in the oncogenetic panel of patients (34 genes). Results: Among the 223 patients analyzed within the scope of the study, 195 had breast cancer, and 28 had ovarian cancer, resulting in the detection of 15 different pathogenic variants of BRCA1 (%4,9) and BRCA2 (%6,7) genes in 26 (11.6%) patients. In the analysis of 32 oncogenes other than BRCA1 and BRCA2 genes, 26 different pathogenic (P) or likely pathogenic (LP) variants were detected in a total of 35 patients (15.7%). Based on the analysis of 223 breast/ ovarian cancer patients together, 41 different pathogenic (P) or likely pathogenic (LP) variants were found in 61 patients (27.3%). Furthermore, 65 different VUSs (Variant of Uncertain Significance) were detected in 73 patients (32.7%). Conclusion: This is the first study to be conducted in our region in a single center located in the Black Sea region. The study was conducted in a single center within the Black Sea region and, to our knowledge, provides the first data in this region in terms of cancer genes other than BRCAs. To appreciate of the genetic susceptibility spectrum of hereditary breast and/or ovarian cancer better, it is imperative to clarify the risks associated with genes other than BRCAs, which carry a high risk for other breast and ovarian cancers, as well as BRCA1 and BRCA2. Therefore, patients in the risk group must undergo multigene panel testing in addition to routine BRCA1 and BRCA2 gene testing. We detected two novel variants in the BRCA2 gene and five novel variants other than BRCA oncogenes. Furthermore, the results of this study contributed to the development of our country's specific variant pool.

Keywords:

ngs, brca1, chek2, Breast/Overian cancer,

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