The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants
| Autor: | Ursula Hille-Betz, Hannah Wallaschek, Marcel Tauscher, Jana Lisa van Luttikhuizen, Karl Hackmann, Judith Penkert, Winfried Hofmann, Brigitte Schlegelberger, Doris Steinemann, Evelin Schröck, Thomas Illig, C Scholz, Bernd Auber, Stephanie Schubert, Colin F. Davenport, Janin Bublitz, Gunnar Schmidt, Lena Wendeburg |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research Adolescent Cancer-Predisposing Gene PALB2 DNA Mutational Analysis Breast Neoplasms Biology Breast Neoplasms Male Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine FANCG medicine PMS2 Humans Genetic Testing HRAS FANCM Medical History Taking skin and connective tissue diseases CHEK2 Aged BRCA2 Protein Ovarian Neoplasms BRCA1 Protein DNA Helicases Middle Aged medicine.disease Oncology 030220 oncology & carcinogenesis Cancer research Hereditary Breast and Ovarian Cancer Syndrome Female Ovarian cancer |
| Zdroj: | International Journal of Cancer. 144:2683-2694 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.31992 |
| Popis: | NGS-based multiple gene panel resequencing in combination with a high resolution CGH-array was used to identify genetic risk factors for hereditary breast and/or ovarian cancer in 237 high risk patients who were previously tested negative for pathogenic BRCA1/2 variants. All patients were screened for pathogenic variants in 94 different cancer predisposing genes. We identified 32 pathogenic variants in 14 different genes (ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C and NBN) in 30 patients (12.7%). Two pathogenic BRCA1 variants that were previously undetected due to less comprehensive and sensitive methods were found. Five pathogenic variants are novel, three of which occur in genes yet unrelated to hereditary breast and/or ovarian cancer (FANCG, FH and HRAS). In our cohort we discovered a remarkably high frequency of truncating variants in FANCM (2.1%), which has recently been suggested as a susceptibility gene for hereditary breast cancer. Two patients of our cohort carried two different pathogenic variants each and 10 other patients in whom a pathogenic variant was confirmed also harbored a variant of unknown significance in a breast and ovarian cancer susceptibility gene. We were able to identify pathogenic variants predisposing for tumor formation in 12.3% of BRCA1/2 negative breast and/or ovarian cancer patients. |
| Databáze: | OpenAIRE |
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