Neslihan DUZKALE, Aysun GÖKCE, Tülay EREN, Gökşen İnanç İMAMOĞLU, Mustafa ALTINBAŞ

BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye'den tek merkez deneyimi

Amaç: Meme kanserlerinin yaklaşık %10'unun kalıtsal olduğu ve bunların yaklaşık %20'sinden BRCA1/2 genlerinin sorumlu olduğu bilinmektedir. Yapılan araştırmalar, meme kanserinde BRCA1/2 dışındaki birçok genin mutasyonlarının da yatkınlığa neden olduğunu göstermiştir. Bu çalışmada meme kanserli Türk kadınlarda diğer kanser yatkınlık genlerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Bu retrospektif çalışmaya Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi Genetik Bölümü'nde 2016-2021 yılları arasında değerlendirilen 66 kadın hasta dahil edildi. Hastaların kansere yatkınlık genleri, yeni nesil dizileme tekniği (NGS) kullanılarak incelendi. Bulgular: Hastaların ortalama tanı yaşı 43 ± 8.0 idi. Genetik analiz ile 66 hastanın 9'unda (%13,63) nedensel gen tespit edildi. Bu genler ATM (%13), CHEK2 (%36), FANCC (%13), MUTYH (%13) ve PALB2'dir (%25). Nedensel varyantı olan hastalar ve diğerleri gruplandırılarak tanı yaşı, tümör lokalizasyonu, tümörün histopatolojik tipi, östrojen/progesteron reseptör durumu, cerbb2, evre, tanı anındaki metastaz ve kanserli akraba sayısı gibi parametreler açısından karşılaştırıldı. Gruplar arasında istatistiksel bir ilişki bulunamadı. Sonuç: Bu çalışmada meme kanserli Türk kadınlarında BRCA1/2 dışındaki kansere yatkınlık genlerinin nedensel varyantlarının saptanma oranı %13,63 olarak belirlendi. Kanserli bireylerde NGS ile çoklu gen testlerinin yapılması, taşıyıcı bireylerin doğru tanı ve uygun tedavi almalarını ve gerekli taramalara yönlendirilmelerini sağlayacaktır.

Anahtar Kelimeler:

Meme kanseri, BRCA1/2, kalıtsal kanser yatkınlık genleri, yeni nesil dizileme, çoklu gen paneli

Investigation of genotype-phenotype relationship in women with BRCA1/2 normal breast cancer: A single-center experience from Turkey

Aim: It is known that approximately 10% of breast cancers are hereditary, and BRCA1/2 genes are responsible for approximately 20% of these. Studies have shown that mutations of many genes other than BRCA1/2 in breast cancer also cause this predisposition. In this study, it was aimed to investigate other causative cancer susceptibility genes in women with breast cancer. Material and Methods: In this retrospective study, 66 female patients who were evaluated in Ankara Dışkapı Yıldırım Beyazıt Training and Research Hospital Genetics Department between 2016-2020 were included. Cancer susceptibility genes of the patients were examined using next-generation sequencing technique (NGS). Results: Mean age at diagnosis of the patients was 43 ± 8.0. By genetic analysis, causative genes were identified in 9 (13.63%) of 66 patients. These genes are ATM (%11), BRIP1 (%11), CHEK2 (%34), FANCC (%11), MUTYH (%11) and PALB2 (%22). Patients with a causal variant and others were grouped, and compared in terms of parameters such as age at diagnosis, tumor localization, histopathological type of tumor, estrogen/progesterone receptor status, c-erbB2, stage, metastasis at diagnosis, and number of relatives with cancer. No statistical relationship was found between the groups. Conclusion: This study determined the rate of detection of causal variants of cancer susceptibility genes other than BRCA1/2 in women with breast cancer who applied to the medical genetics department as 13.63%. Performing multiple gene tests with the NGS in cancer individuals will allow carrier individuals to receive correct diagnosis and appropriate treatment and to be directed to necessary screenings.

Keywords:

Breast cancer, BRCA1/2, hereditary cancer susceptibility genes, next generation sequencing, multi-gene panel,

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