Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey

被引:7
作者
Bora, Elcin [1 ]
Caglayan, Ahmet Okay [1 ]
Koc, Altug [1 ]
Cankaya, Tufan [1 ]
Ozkalayci, Hande [1 ]
Kocabey, Mehmet [1 ]
Kemer, Demet [1 ]
Aksoy, Suleyman [2 ]
Alicikus, Zumre Arican [3 ]
Akin, Isil Basara [4 ]
Durak, Merih Guray [5 ]
Gurel, Duygu [5 ]
Yavuzsen, Tugba [6 ]
Sevinc, Ali [2 ]
Somali, Isil [6 ]
Gorken, Ilknur [3 ]
Balci, Pinar [4 ]
Karaoglu, Aziz [6 ]
Saydam, Serdar [2 ]
Ulgenalp, Ayfer [1 ]
机构
[1] Dokuz Eylul Univ, Sch Med, Dept Med Genet, Izmir, Turkey
[2] Dokuz Eylul Univ, Sch Med, Dept Gen Surg, Izmir, Turkey
[3] Dokuz Eylul Univ, Sch Med, Dept Radiat Oncol, Izmir, Turkey
[4] Dokuz Eylul Univ, Sch Med, Dept Radiol, Izmir, Turkey
[5] Dokuz Eylul Univ, Sch Med, Dept Pathol, Izmir, Turkey
[6] Dokuz Eylul Univ, Sch Med, Dept Oncol, Izmir, Turkey
关键词
BRCA1; BRCA2; Breast Cancer; MLPA; Next generation sequencing; OVARIAN-CANCER; TURKISH BREAST; GENOMIC REARRANGEMENTS; BREAST/OVARIAN CANCER; GERMLINE MUTATIONS; MEDICAL GENETICS; AMERICAN-COLLEGE; BRCA2; MUTATIONS; RISK; VARIANTS;
D O I
10.1016/j.cancergen.2022.02.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly.In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis. (c) 2022 Published by Elsevier Inc.
引用
收藏
页码:118 / 133
页数:16
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