Cancer is a genetic condition driven by a series of both inherited (germline) and tumour specific (somatic) mutations. The analysis of tumour to identify somatic alterations and generate a genetic profile has given rise to a personalised approach for treating oncology patients, guiding optimal therapy. Next generation sequencing (NGS) technology is now routinely utilised in oncology to screen for both genes known to be associated with improving treatment response, as well as, genes of uncertain significance to contribute to new findings in cancer treatment. In the development of genome wide mutation analysis of tumour tissue, germline DNA has also been routinely collected for comparative analysis in order to identity tumour specific mutations. As the identification of germline mutations is secondary to the main purpose of tumour testing for targeted treatment, the management of germline findings has been extensively debated, in particular, around if and when to communicate these findings to patients. The role of the genetic counsellor in this process has been pertinent to these discussions. Clinical practice, however, is shifting towards a preference of sequencing tumour tissue alone to characterise its molecular profile for reasons such as reducing cost and facilitating logistics of sample collection. This method raises the question of how the testing of tumour alone contributes to the identification of germline mutations. The laboratory at POLARIS, Singapore, has generated genomic data of 130 colon tumours using a panel of 84 genes, including 29 germline susceptibility genes associated with known inherited syndromes. The analysis of this data has given an insight into the proportion of mutations that are potentially germline, which in turn will impact how patients are consented for tumour profiling and the delivery of the results. In generating these findings, however, the analysis process has demonstrated a number of the complexities in interpreting the pathogenicity of the variants, as well as, determining the somatic or germline origin of the variant. The challenges in interpreting germline mutations from tumour next generation data, the importance of conveying a germline finding to the patient and the integration of the genetic counsellor in this process will be discussed.
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