BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome

INTRODUCTION: Breast cancer is the most frequently diagnosed female cancer according to the 2020 data of the World Health Organization. It is mostly sporadic, 5-10% of which occur on the basis of genetic predisposition. In this study, we aimed to detect mutations in BRCA and non-BRCA genes in patients admitted with the diagnosis of breast cancer and/or ovarian cancer, and to identify mutations with increased frequency and variants specific to the Turkish population.
METHODS: 120 patients who applied to Balýkesir Atatürk City Hospital Medical Genetics Department between 01.01.2019-01.08.2021 and had hereditary Breast and/or Ovarian Cancer molecular genetic study criteria were included in this study. First, BRCA1/2 genes next-generation sequencing were performed on these patients, respectively. BRCA1 and BRCA2 gene deletion duplication analysis and/or multiple gene panel associated with cancer susceptibility were studied from patients with no mutations.
RESULTS: In this study, molecular genetic susceptibility study associated with Hereditary Breast and/or Ovarian Cancer 33,33 % positive variants were found in BRCA and non-BRCA genes. BRCA1/2 mutations were detected in 20 patients. In addition, non-BRCA mutations (ATM, CHEK2, RAD50, RAD51D, STK11, SDHA, RB1, POLD1, SMAD4, CDH1 and CDKN22 genes) were detected in 20 patients. We identified a total of 7 new variants in the BRCA2, ATM, RAD50, RAD51D, STK11 and POLD1 genes.
DISCUSSION AND CONCLUSION: Clarification of risks specific to non-BRCA genes is necessary for a better understanding of the HBOC genetic susceptibility spectrum. Therefore, multi-gene panel testing is needed after routine BRCA genes. In our study, most of the novel mutations were detected in non-BRCA genes. In addition, two novel BRCA variants have been reported. It also contributed to the identification of mutations specific to the Turkish population.

Kalýtsal Meme ve/veya Over Kanseri Sendromlu Olgularda Yeni Nesil Dizileme ile Saptanan BRCA ve non-BRCA Varyantlar

GÝRÝÞ ve AMAÇ: Meme kanseri Dünya Saðlýk Örgütü’nün 2020 yýlý verilerine göre en sýk taný alan kadýn kanseridir. Çoðunlukla sporadik olmakla birlikte %5-10 oranýnda genetik yatkýnlýk zemininde ortaya çýkar. Meme kanseri ve/ veya over kanseri tanýsýyla baþvuran hastalardaki genetik yatkýnlýðý araþtýrdýðýmýz bu çalýþmamýzda amacýmýz BRCA ve non-BRCA genlerinde saptadýðýmýz varyantlarý sunmak ve Türk popülasyonuna özgü mutasyonlarý belirmektir.
YÖNTEM ve GEREÇLER: 01.01.2019-01.08.2021 tarihleri arasýnda Balýkesir Atatürk Þehir Hastanesi Týbbi Genetik polikliniðine baþvuran Herediter Meme ve/ veya Over Kanseri moleküler genetik çalýþma kriterlerini karþýlayan 120 hasta çalýþmaya dahil edildi. Öncelikle sýrasýyla BRCA1 ve BRCA2 geni dizi analizi çalýþýldý. BRCA1/2 tüm gen dizi analizi yöntemiyle mutasyon tespit edilmeyen hastalardan BRCA1 ve BRCA2 geni delesyon dublikasyon analizi ve/ veya kansere yatkýnlýkla iliþkilendirilen çoklu gen paneli çalýþýldý.
BULGULAR: Herediter Meme ve/veya Over Kanseri ile iliþkili genetik etyolojiyi araþtýrdýðýmýz bu çalýþmada BRCA ve non-BRCA genlerde %33,33 pozitif varyant saptandý. 20 hastada BRCA1 ve BRCA2 genlerinde, 20 hastada ise non-BRCA genlerinde (ATM, CHEK2, RAD50, RAD51D, STK11, MSH6, SDHA, RB1, POLD1, SMAD4, CDH1 ve CDKN22) mutasyon tespit edildi. BRCA2, ATM, RAD50, RAD51D, STK11 ve POLD1 genlerinde olmak üzere toplam 7 novel varyant tanýmlandý.
TARTIÞMA ve SONUÇ: HBOC genetik duyarlýlýk spektrumunun daha iyi anlaþýlmasý için non-BRCA genlerine özgü risklerin aydýnlatýlmasý gerekmektedir. Bu nedenle rutin BRCA genlerinden sonra çoklu gen panel testine ihtiyaç vardýr. Çalýþmamýzdaki, yeni mutasyonlarýn çoðu non-BRCA genlerinde tespit edildi. Ek olarak, iki yeni BRCA varyantý raporlandý. Ayrýca bu çalýþma ile Türk popülasyonuna özgü mutasyonlarýn belirlenmesine de katký saðlandý.