Publication: Ailesel meme kanseri hastalarında kalıtsal genlerin yeni nesil dizileme yöntemi ile dizilenmesi ve telomer uzunluğuyla ilişkisi
Abstract
Ailesel Meme Kanseri Hastalarında Kalıtsal Genlerin Yeni Nesil Dizileme Yöntemi ile Dizilenmesi ve Telomer Uzunluğuyla İlişkisiAmaç: Kalıtsal meme kanserinin en yaygın sebebi, meme kanseri geni-1 ve 2 (BRCA1 ve BRCA2) genlerinde kalıtılan mutasyonlardır. BRCA1 ve BRCA2 genleri, meme kanserinin yaygınlığı nedeniyle, günümüzde en fazla dizilenen genler arasındadır. Bu çalışmada, erken yaşta meme kanseri gelişen hastalarda ve meme kanseri gelişme riski taşıyan bireylerde yeni nesil dizileme yöntemi ile BRCA1/ 2 genlerindeki mutasyonları belirlemek ve telomer uzunluğu ile arasındaki ilişkiyi değerlendirmek hedeflenmiştir.Gereç ve Yöntem: Hastalardan edinilen kan örneklerinden DNA izolasyonu sonrası yeni nesil dizileme yöntemiyle BRCA1 ve BRCA2 geni dizilemesi ve gerçek zamanlı PZR reaksiyonu ile telomer uzunluğu ölçümü gerçekleştirilmiştir.Bulgular: 113 bireyden oluşan hasta ve yüksek risk grubunda, 66 örnekte (%58,4) BRCA1 ve/ veya BRCA2 geninde herhangi bir mutasyon belirlenememiş, diğer 47 örnekte (%41,6), 31 BRCA2 geni mutasyonu ve 21 BRCA1 geni mutasyonu tanımlanmıştır. Hastaların telomer uzunlukları ile mutasyon varlığı karşılaştırıldığında, mutasyon taşıyan bireylerin, yaş eşlesmesi yapılan mutasyon taşımayan bireylerden istatistiksel olarak anlamlı derecede kısa olduğu bulunmuştur. Sonuçlar: Elde ettiğimiz bulgular meme kanseri gelşme riski yüksek olan bireylerde BRCA1 ve BRCA2 genlerinin mutasyonel analizinin önemini göstermektedir. BRCA1 ve BRCA2 geninde mutasyon taşıyan kişilerin, taşımayanlara göre daha kısa telomer uzunluğuna sahip olması, BRCA1 ve BRCA2 genlerinin telomer uzunluğu mekanizmasında rol aldığı yönündeki bulguları desteklemektedir.
Sequencing Hereditary Genes with Next Generation Sequencing Method in Familial Breast Cancer Patients and Their Relation with Telomere Length Objective: The most common cause of hereditary breast cancer is the mutations inherited in the genes of breast cancer gene-1 and 2 (BRCA1 and 2). These genes are among the most sequenced genes due to the prevalence of breast cancer. It was aimed to determine mutations in BRCA1/ 2 genes by the next generation sequencing method and to evaluate the relationship between telomere length in patients who develop early breast cancer and who are at risk of developing breast cancer. Materials and Methods: After DNA isolation from the blood samples obtained by the patients, BRCA1 and BRCA2 gene sequencing by the next generation sequencing method and telomere length measurement with real-time PCR reaction were performed. Results: No mutation was detected in the BRCA1 and/ or BRCA2 gene in 66 patients (58.4%) in the patient and high-risk group consisting of 113 individuals, and in 47 other samples (41.6%), 31 BRCA2 gene mutations and 21 BRCA1 gene mutations were identified. When mutation status were compared with telomere length, it was found that the individuals carrying a mutation in either BRCA1 and/ or BRCA2 gene were shorter than those who did not carry the mutation and this result was statistically significant. Conclusion: Our findings indicate the importance of mutational analysis of BRCA1 and BRCA2 genes in individuals with high risk of developing breast cancer. The shorter telomere length of BRCA1 and BRCA2 gene mutants compared to non-mutants supports the findings that BRCA1 and BRCA2 genes play a role in the telomere length mechanism.
Sequencing Hereditary Genes with Next Generation Sequencing Method in Familial Breast Cancer Patients and Their Relation with Telomere Length Objective: The most common cause of hereditary breast cancer is the mutations inherited in the genes of breast cancer gene-1 and 2 (BRCA1 and 2). These genes are among the most sequenced genes due to the prevalence of breast cancer. It was aimed to determine mutations in BRCA1/ 2 genes by the next generation sequencing method and to evaluate the relationship between telomere length in patients who develop early breast cancer and who are at risk of developing breast cancer. Materials and Methods: After DNA isolation from the blood samples obtained by the patients, BRCA1 and BRCA2 gene sequencing by the next generation sequencing method and telomere length measurement with real-time PCR reaction were performed. Results: No mutation was detected in the BRCA1 and/ or BRCA2 gene in 66 patients (58.4%) in the patient and high-risk group consisting of 113 individuals, and in 47 other samples (41.6%), 31 BRCA2 gene mutations and 21 BRCA1 gene mutations were identified. When mutation status were compared with telomere length, it was found that the individuals carrying a mutation in either BRCA1 and/ or BRCA2 gene were shorter than those who did not carry the mutation and this result was statistically significant. Conclusion: Our findings indicate the importance of mutational analysis of BRCA1 and BRCA2 genes in individuals with high risk of developing breast cancer. The shorter telomere length of BRCA1 and BRCA2 gene mutants compared to non-mutants supports the findings that BRCA1 and BRCA2 genes play a role in the telomere length mechanism.