Precision medicine in heritable cancer: when somatic tumour testing and germline mutations meet

Abstract

Cancer is among the leading causes of death and disfigurement worldwide with an estimated global incidence of 14 million and ~8.2 million cancer-related deaths per annum. An estimated 5-10% of all cancers are hereditary, meaning a single gene mutation contributed to development of the cancer. In other words, inherited cancer has a worldwide incidence of ~1.4 million new cases per annum and a global prevalence of 300 million, and are often poorly recognised. The increase in genetic sequencing capability combined with the decrease in the cost of testing has altered both regulatory policy and clinical oncology practice Well-known examples of clinically important cancer susceptibility syndromes such as those caused by genetic mutations in highly penetrant genes such as BRCA1/2 hereditary breast-ovarian cancer syndrome genes have provided the framework for the practice of clinical cancer genetics. There is no question that these tests have provided clinical benefit to the patient and her/his family. However, with the expanding role of next generation sequencing in tumour profiling as well as in germline testing, clinicians are now faced with significant new challenges and potentially unexpected opportunities. Issues such as determining how best to deal with gene variants of uncertain clinical significance and the issue of incidental findings of hereditary cancer risk may be encountered during tumour genomic testing will require a concerted effort and dialogue on the part of the broad genomic community.