Isparta Bölgesinde Meme ve/veya Over Kanseri Riski Taşıyan Hastalarda BRCA1 ve BRCA2 Gen Mutasyonlarının Yeni Nesil Dizileme Yöntemi ile Belirlenmesi

Year 2021, Volume: 5 Issue: 1, 74 - 79, 03.04.2021

Muhammet Yusuf Tepebaşı , Kuyaş Hekimler Öztürk , Halil Özbaş , Pinar Aslan Kosar

https://doi.org/10.29058/mjwbs.798994

Abstract

Amaç: Tümör baskılayıcı genler BRCA1 ve BRCA2, meme ve / veya over kanserlerinde tarama ve
teşhis için kullanılmaktadır. BRCA1 / BRCA2 genleri bu hastalıkların % 20-25’i ile ilişkilidir. BRCA1
ve BRCA2 gen mutasyonlarının spektrumu ve prevalansı her popülasyonda farklıdır. Duyarlılık
genlerindeki patojenik mutasyonların prevalansını belirlemek ve yeni mutasyonları tanımlamak ulusal
sağlık politikaları geliştirmek için önemlidir. Bu retrospektif çalışmada, Isparta bölgesinde meme / veya
over kanser şüphesi ile 2018-2020 yılları arasında Süleyman Demirel Üniversitesi Tıp Fakültesi Tıbbi
Genetik Kliniği’ne başvuran hastaların BRCA1/2 genlerindeki mutasyonlar araştırılmıştır.
başvuran 76 hastanın Yeni Nesil Dizileme (NGS) yöntemi ile BRCA1 ve BRCA2 gen mutasyon analizleri yapılmıştır.
Bulgular: Verileri değerlendirmelerimiz sonucunda, BRCA1 geninde 4 patojenik, 1 muhtemel patojenik, 5 önemi bilinmeyen varyant (VUS) ve 11 benign varyant tespit edildi. Ayrıca BRCA2 geninde 3 patojenik, 3 VUS, 11 benign ve 1 yeni varyant tespit edildi.
Sonuç: Çalışmamızın sonucunda elde ettiğimiz verilerin BRCA1 ve BRCA2 gen mutasyonlarının prevalansının belirlenmesine ve meme ve/ veya over kanserinin saptanmasına katkıda bulunacağına inanıyoruz.

Keywords

BRCA1 ve BRCA2 gen, meme ve/veya over kanseri, yeni nesil dizileme

Determination of BRCA1 and BRCA2 Gene Mutations in Patients at Risk of Breast and/or Ovarian Cancer by Next Generation Sequencing in the Isparta Region

Abstract

and/or ovarian cancers. BRCA1 / BRCA2 genes are associated with 20-25% of these diseases. The
spectrum and prevalence of BRCA1 and BRCA2 gene mutations are different in each population.
Determining the prevalence of pathogenic mutations in susceptibility genes and identifying new
mutations are important for developing national health policies. In this retrospective study, mutations
in the BRCA1 / 2 genes of patients who applied to Süleyman Demirel University Faculty of Medicine
Medical Genetics Clinic between 2018-2020 with the suspicion of breast / or ovarian cancer in the
Isparta region were investigated.
Material and Methods: In our study, BRCA1 and BRCA2 gene mutation analyzes were performed by
Next Generation Sequencing (NGS) method in 76 patients who applied to the Medical Genetics Clinic
with the indication of breast cancer, breast mass, family history, and ovarian cancer.
Results: As a result of our data analysis, 4 pathogenic, 1 likely pathogenic, 5 variants of unknown
significance (VUS), and 11 benign variants were detected in the BRCA1 gene. Also, 3 pathogenic, 3
VUS, 11 benign, and 1 new variant were detected in the BRCA2 gene.
Conclusion: We believe that the results of our study will contribute to the determination of the prevalence
of BRCA1 and BRCA2 gene mutations and the detection of breast and/or ovarian cancer.

Keywords

BRCA1 and BRCA2 gene, breast and/or ovarian cancer, next generation sequencing

References

• 1. Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev 2016;17(S3):43-46.
• 2. Laitman Y, Friebel TM, Yannoukakos D, Fostira F, Konstantopoulou I, Figlioli G, Bonanni B, Manoukian S, Zuradelli M, Tondini C, Pasini B, Peterlongo P, Plaseska- Karanfilska D, Jakimovska M, Majidzadeh K, Zarinfam S, Loizidou MA, Hadjisavvas A, Michailidou K, Kyriacou K, Behar . The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries. Hum Mutat 2019;40(11):e1-e23.
• 3. Egeli U, Cecener G, Tunca B, Tasdelen I. Novel germline BRCA1 and BRCA2 mutations in Turkish women with breast and/or ovarian cancer and their relatives. Cancer Invest 2006;24(5):484-491.
• 4. Ueland FR. A perspective on ovarian cancer biomarkers: past, present and yet-to-come. Diagnostics 2017;7(1):14.
• 5. Yazıcı H, Kılıç S, Akdeniz D, Şükrüoğlu Ö, Tuncer ŞB, Avşar M, Kuru G, Çelik B, Küçücük S, Saip P. Frequency of rearrangements versus small indels mutations in BRCA1 and BRCA2 genes in turkish patients with high risk breast and ovarian cancer. Eur J Breast Health 2018;14(2):93-99.
• 6. Akkuzu MZ, Küçüköner M, Irtegun S, Akdeniz N, URAKÇI Z, Kaplan MA, Büyükbayram H, Işıkdoğan A. Meme Kanserinde Brca-1 ve Brca-2’de Sık Görülen Polimorfizm Mutasyonların Bölgemizde Varlığı. Dicle Tıp Dergisi 2019;46(4):623-631.
• 7. Mehrgou A, Akouchekian M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J Islam Repub Iran 2016;30:369.
• 8. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994;266(5182):66-71.
• 9. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995;378(6559):789-792.
• 10. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003;302(5645):643-646.
• 11. Gorski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J, Pluzańska A, Bebenek M, Fischer-Maliszewska L, Grzybowska E, Narod SA, Lubiński J. Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. Am J Hum Genet 2000;66(6):1963-1968.
• 12. Tereschenko IV, Basham VM, Ponder BA, Pharoah PD. BRCA1 and BRCA2 mutations in Russian familial breast cancer. Hum Mutat 2002;19(2):184-188.
• 13. Anagnostopoulos T, Pertesi M, Konstantopoulou I, Armaou S, Kamakari S, Nasioulas G, Athanasiou A, Dobrovic A, Young MA, Goldgar D, Fountzilas G, Yannoukakos D. G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: Evaluation of its pathogenicity and inferences on its genealogical history. Breast Cancer Res Treat 2008;110(2):377- 385.
• 14. Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N, Peretz T. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 1997;60(3):505-514.
• 15. Bruchim Bar-Sade R, Kruglikova A, Modan B, Gak E, Hirsh- Yechezkel G, Theodor L, Novikov I, Gershoni-Baruch R, Risel S, Papa MZ, Ben-Baruch G, Friedman E. The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim. Human molecular genetics 1998;7(5):801-805.
• 16. Shiri-Sverdlov R, Gershoni-Baruch R, Ichezkel-Hirsch G, Gotlieb WH, Bar-Sade RB, Chetrit A, Rizel S, Modan B, Friedman E. The Tyr978X BRCA1 mutation in non-Ashkenazi Jews: Occurrence in high-risk families, general population and unselected ovarian cancer patients. Community Genet 2001;4(1):50-55.
• 17. Berman DB, Costalas J, Schultz DC, Grana G, Daly M, Godwin AK. A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals. Cancer Res 1996;56(15):3409-3014.
• 18. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: Public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 2013;42(D1):D980-D985.
• 19. Karami F, Mehdipour P. A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. Biomed Res Int 2013;2013:928562.
• 20. Csokay B, Tihomirova L, Stengrevics A, Sinicka O, Olah E. Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Hum Mutat 1999;14(1):92.
• 21. Hamel N, Feng B-J, Foretova L, Stoppa-Lyonnet D, Narod SA, Imyanitov E, Sinilnikova O, Tihomirova L, Lubinski J, Gronwald J, Gorski B, v O Hansen T, Nielsen FC, Thomassen M, Yannoukakos D, Konstantopoulou I, Zajac V, Ciernikova S, Couch FJ, Greenwood CMT, Goldgar DE, Foulkes WD. On the origin and diffusion of BRCA1 c. 5266dupC (5382insC) in European populations. Eur J Hum Genet 2011;19(3):300-306.
• 22. de Juan Jiménez I, Casado ZG, Suela SP, Cardeñosa EE, Guerrero JAL, Huerta ÁS, González IC, Heras ABS, Fita MJJ, García IT, Ponce CG, de Dueñas EM, Noguera IR, Trejo DS, Sáez MG, Gilabert PB. Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence. Fam Cancer 2013;12(4):767-777.
• 23. Bahsi T, Erdem HB. Spectrum of BRCA1/BRCA2 variants in 1419 Turkish breast and ovarian cancer patients: a single center study. Turkish Journal of Biochemistry 2019;45(1):83- 90.