Hereditary Cancer Syndromes and Inherited Cancer Risks

Abstract

Genetic testing for hereditary cancer syndromes and acquired malignancies is a routine part of personalized cancer treatment. Identifying germline variants for hereditary cancer syndromes and predisposition risks of non-hematologic and hematologic malignancies provide invaluable information for future screening for both patients and family members. Although different methodologies have been utilized, the application of next-generation sequencing technology, either using gene panels, exome sequencing, or whole-genome sequencing, has primarily replaced sequential single gene testing. Massively parallel sequencing has permitted the analysis of multiple genes at the same time and became an affordable mean in clinical practice to increase the possibility of finding the causal mutation while reducing the amount and ultimately cost of diagnostic testing. Differentiating between germline variants and tumor-associated somatic mutations is important in the clinical interpretation of molecular sequencing results, guiding confirmatory germline testing, and expediting appropriate genetic counseling. These concepts, highlighted by several cases are included in the second part of the chapter. Seven presented cases illustrate the process of assessing genetic variants of hereditary cancer syndromes with respect to family history and tumor-associated somatic testing. Identifying cancer-predisposing pathogenic variants benefit patients by personalizing their medical management, including surveillance, early preventive interventions, and modification of treatment strategies, and it also facilitates identification of at risk family members.