Yıl: 2022 Cilt: 55 Sayı: 2 Sayfa Aralığı: 77 - 84 Metin Dili: İngilizce DOI: 10.5505/aot.2022.82246 İndeks Tarihi: 21-09-2022

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

Öz:
Introduction: Breast cancer is the most frequently diagnosed female cancer according to the 2020 data of the World Health Organization. It is mostly sporadic, 10-15% 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. Materials and methods: Between January 2019 and August 2021, 120 patients who applied to our clinic with hereditary Breast and/or Ovarian Cancer meeting the genetic test study criteria were included in the 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 molecular genetic susceptibility study associated with Hereditary Breast and/or Ovarian Cancer, 33.3 % 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: Clarification of risks specific to non-BRCA genes is necessary for a better understanding of the Hereditary Breast and/or Ovarian Cancer Syndrome (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.
Anahtar Kelime:

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

Öz:
Giriş ve Amaç: Meme kanseri Dünya Sağlık Örgütü’nün 2020 yılı verilerine göre en sık tanı alan kadın kanseridir. Çoğunlukla sporadik olmakla birlikte %10-15 oranında genetik yatkınlık zemininde ortaya çıkar. Meme kanseri ve/veya over kanseri tanısıyla başvuran hastalardaki genetik yatkınlığı araştırdığımız bu çalışmamızda amacımız BRCA ve non-BRCA genlerinde saptadığımız varyantları sunmak ve Türk popülasyonuna özgü mutasyonları belirmektir. Yöntem ve Gereçler: Ocak 2019-Agustos 2021 tarihleri arasinda klinigimize kalitsal Meme ve/veya Yumurtalik Kanseri ile basvuran, genetik test calisma kriterlerini karsilayan 120 hasta calismaya dahil edildi. Öncelikle sırasıyla BRCA1 ve BRCA2 geni dizi analizi çalışıldı. BRCA1/2 tüm gen dizi analizi yöntemiyle mutasyon tespit edilmeyen hastalardan BRCA1 ve BRCA2 geni delesyon dublikasyon analizi ve/ veya kansere yatkınlıkla ilişkilendirilen çoklu gen paneli çalışıldı. Bulgular: Herediter Meme ve/veya Over Kanseri ile ilişkili genetik etyolojiyi araştırdığımız bu çalışmada BRCA ve non-BRCA genlerde %33.3 pozitif varyant saptandı. 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 tanımlandı. Tartışma ve Sonuç: Herediter Meme ve/veya Over Kanseri genetik duyarlılık spektrumunun daha iyi anlaşılması için non-BRCA genlerine özgü risklerin aydınlatılması gerekmektedir. Bu nedenle rutin BRCA genlerinden sonra çoklu gen panel testine ihtiyaç vardır. Çalışmamızdaki, yeni mutasyonların çoğu non-BRCA genlerinde tespit edildi. Ek olarak, iki yeni BRCA varyantı raporlandı. Ayrıca bu çalışma ile Türk popülasyonuna özgü mutasyonların belirlenmesine de katkı sağlandı.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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  • 1.Marmolejo DH, Wong MYZ, Bajalica-Lagercrantz S, et al. Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe. European Journal of Medical Genetics. 2021: 104350.
  • 2.World Health Organization International Agency for Research on Cancer. The global cancer observatory. 2020 statistics. Available from: https:// gco.iarc.fr /today/ online-analysis-multi-bars.
  • 3.Mallen AR, Townsend MK, Tworoger SS. Risk factors for ovarian carcinoma. Hematology/Oncology Clinics. 2018;32: 891-902.
  • 4.Mittal A, Deo SVS, Gogia A, et al. Profile of pathogenic mutations and evaluation of germline genetic testing criteria in consecutive breast cancer patients treated at a North Indian tertiary care center. Annals of Surgical Oncology. 2021: 1-10.
  • 5. 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. 2020; 45: 83-90.
  • 6. Judkins T, Rosenthal E, Arnell C, et al. Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer. 2012;118: 5210-5216.
  • 7. Miramar MD, Calvo MT, Rodriguez A, et al. Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1. Breast Cancer Research and Treatment. 2008;112: 353-358.
  • 8. Thirthagiri E, Lee SY, Kang P, et al. Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Research. 2008;10: 1-12.
  • 9. Karami F., Mehdipour P. A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. BioMed research international. 2013.
  • 10.Teker ND, Eyerci N. Double Heterozygous Mutations in the BRCA2 and ATM Genes: A Case Report and Review of the Literature. Breast Care. 2021;16: 412-417.
  • 11.Tedaldi G, Tebaldi M, Zampiga V, et al. Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer. Oncotarget. 2017;8: 47064-47075
  • 12.Pinto P, Paulo P, Santos C, et al. Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic hetero-geneity. Breast cancer research and treatment. 2016; 159: 245-256.
  • 13.Tung N, Lin NU, Kidd J, et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. Journal of Clinical Oncology. 2016;34: 1433-1455.
  • 14.Hall MJ, Reid JE, Burbidge LA, et al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast ovarian cancer. Cancer, 2009;115: 2222-2233.
  • 15.LaDuca H, Stuenkel AJ, Dolinsky JS, et al. Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genetics in medicine. 2014;16: 830-837.
  • 16.Pashayan N, Antoniou AC, Ivanus U, et al. Personalized early detection and prevention of breast cancer: ENVISION consensus statement. Nature Reviews Clinical Oncology. 2020;17: 687-705.
  • 17. Goetz MP, Gradishar WJ, Anderson BO, et al. NCCN Guidelines Insights: Breast Cancer, Version 3.2018. J Natl Compr Canc Netw. 2019;17(2):118-126.
  • 18.Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17: 405–24
  • 19.Yazici H, Bitisik O, Akisik E, et al. BRCA1 and BRCA2 mutations in Turkish breast/ ovarian families and young breast cancer patients. British Journal of Cancer. 2000;83: 737-742.
  • 20.Cecener G, Takanlou LB, Takanlou MS, et al. Clinicopathologic Features and Genetic Characteristics of the BRCA1/2 Mutation in Turkish Breast Cancer Patients. Journal Pre-proof. S2210-7762 (19)30335-7.
  • 21. Gezdirici A, Gökpınar İli E, Değirmenci B, et al. Hereditary Breast-Ovarian Cancer and BRCA1/BRCA2 variants: a single center experience. Acta Oncologica Turcica, 54(3), 264-272.
  • 22. Kraus C, Hoyer J, Vasileiou G, et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. International journal of cancer. 2017;140: 95-102.
  • 23. Marabelli M, Cheng SC, Parmigiani G. Penetrance of ATM gene mutations in breast cancer: a meta analysis of different measures of risk. Genetic epidemiology, 2016;40: 425-431.
  • 24.Tung N, Lin NU, Kidd J, et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. Journal of Clinical Oncology. 2016;34: 1460.
  • 25. ClinVar: https://www.ncbi.nlm.nih.gov/clinvar. Accessed 7 Sept 2020.
APA Gerik-Çelebi H, BOLAT H (2022). BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. , 77 - 84. 10.5505/aot.2022.82246
Chicago Gerik-Çelebi Hamide Betül,BOLAT HILMI BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. (2022): 77 - 84. 10.5505/aot.2022.82246
MLA Gerik-Çelebi Hamide Betül,BOLAT HILMI BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. , 2022, ss.77 - 84. 10.5505/aot.2022.82246
AMA Gerik-Çelebi H,BOLAT H BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. . 2022; 77 - 84. 10.5505/aot.2022.82246
Vancouver Gerik-Çelebi H,BOLAT H BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. . 2022; 77 - 84. 10.5505/aot.2022.82246
IEEE Gerik-Çelebi H,BOLAT H "BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome." , ss.77 - 84, 2022. 10.5505/aot.2022.82246
ISNAD Gerik-Çelebi, Hamide Betül - BOLAT, HILMI. "BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome". (2022), 77-84. https://doi.org/10.5505/aot.2022.82246
APA Gerik-Çelebi H, BOLAT H (2022). BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. ACTA ONCOLOGICA TURCICA, 55(2), 77 - 84. 10.5505/aot.2022.82246
Chicago Gerik-Çelebi Hamide Betül,BOLAT HILMI BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. ACTA ONCOLOGICA TURCICA 55, no.2 (2022): 77 - 84. 10.5505/aot.2022.82246
MLA Gerik-Çelebi Hamide Betül,BOLAT HILMI BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. ACTA ONCOLOGICA TURCICA, vol.55, no.2, 2022, ss.77 - 84. 10.5505/aot.2022.82246
AMA Gerik-Çelebi H,BOLAT H BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. ACTA ONCOLOGICA TURCICA. 2022; 55(2): 77 - 84. 10.5505/aot.2022.82246
Vancouver Gerik-Çelebi H,BOLAT H BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome. ACTA ONCOLOGICA TURCICA. 2022; 55(2): 77 - 84. 10.5505/aot.2022.82246
IEEE Gerik-Çelebi H,BOLAT H "BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome." ACTA ONCOLOGICA TURCICA, 55, ss.77 - 84, 2022. 10.5505/aot.2022.82246
ISNAD Gerik-Çelebi, Hamide Betül - BOLAT, HILMI. "BRCA and non-BRCA Variants Detected by Next Generation Sequencing in Patients with Hereditary Breast and/or Ovarian Cancer Syndrome". ACTA ONCOLOGICA TURCICA 55/2 (2022), 77-84. https://doi.org/10.5505/aot.2022.82246