Li-Fraumeni syndrome: not a straightforward diagnosis anymore—the interpretation of pathogenic variants of low allele frequency and the differences between germline PVs, mosaicism, and clonal hematopoiesis

被引：0
作者：
Felipe Batalini
Ellie G. Peacock
Lindsey Stobie
Alison Robertson
Judy Garber
Jeffrey N. Weitzel
Nadine M. Tung
机构：
[1] Harvard Medical School,Division of Hematology and Oncology, Beth Israel Deaconess Medical Center
[2] Dana-Farber Cancer Institute,Center for Cancer Genetics and Prevention
[3] Harvard Medical School,Division of Clinical Cancer Genomics
[4] Dana-Farber Cancer Institute,Cancer Risk and Prevention Program, Beth Israel Deaconess Medical Center
[5] City of Hope Cancer Center,undefined
[6] Harvard Medical School,undefined
来源：
Breast Cancer Research | / 21卷
关键词：
Mutation; Pathogenic variant; TP53; Li-Fraumeni syndrome; Hereditary breast cancer; Clonal hematopoiesis; Mosaicism; Low allele frequency;
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摘要：
The introduction of next-generation sequencing has resulted in testing multiple genes simultaneously to identify inherited pathogenic variants (PVs) in cancer susceptibility genes. PVs with low minor allele frequencies (MAFs) (< 25–35%) are highlighted on germline genetic test reports. In this review, we focus on the challenges of interpreting PVs with low MAF in breast cancer patients undergoing germline testing and the implications for management.
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[1]  
Pharoah Paul D.P.(2002)Polygenic susceptibility to breast cancer and implications for prevention Nature Genetics 31 33-36
[2]  
Antoniou Antonis(1991)Genetic analysis of breast cancer in the cancer and steroid hormone study Am J Hum Genet 48 232-242
[3]  
Bobrow Martin(1988)Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families PNAS Natl Acad Sci 85 3044-3048
[4]  
Zimmern Ron L.(2009)Polygenic susceptibility to breast cancer: current state-of-the-art Future Oncol 5 689-701
[5]  
Easton Douglas F.(2016)Systematic evaluation of Sanger validation of NextGen sequencing variants Clin Chem 62 647-654
[6]  
Ponder Bruce A.J.(2017)Somatic TP53 variants frequently confound germ-line testing results Genetics in Medicine 20 809-816
[7]  
Claus EB(2015)Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk BMC Cancer 15 215-8
[8]  
Risch N(2015)Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes Blood 126 16-1593
[9]  
Thompson WD(2017)Detection of somatic variants in peripheral blood lymphocytes using a next generation sequencing multigene pan cancer panel Cancer Genet 211 5-1468
[10]  
Newman B(2018)Prevalence of clonal hematopoiesis mutations in tumor-only clinical genomic profiling of solid tumors JAMA Oncol 4 1589-3562
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