Clinical cancer genomic profiling

Profiling tumours by next-generation sequencing can improve diagnostic accuracy, assess for heritable cancer risk and guide treatment selection. The authors review efforts to enhance the clinical utility of cancer genomic profiling through integrative analyses of tumour and germline variants, as well as by characterizing allelic context and mutational signatures that influence therapy response. Technological innovation and rapid reduction in sequencing costs have enabled the genomic profiling of hundreds of cancer-associated genes as a component of routine cancer care. Tumour genomic profiling can refine cancer subtype classification, identify which patients are most likely to benefit from systemic therapies and screen for germline variants that influence heritable cancer risk. Here, we discuss ongoing efforts to enhance the clinical utility of tumour genomic profiling by integrating tumour and germline analyses, characterizing allelic context and identifying mutational signatures that influence therapy response. We also discuss the potential clinical utility of more comprehensive whole-genome and whole-transcriptome sequencing and ultra-sensitive cell-free DNA profiling platforms, which allow for minimally invasive, serial analyses of tumour-derived DNA in blood.

Automated summary

Profiling tumors by next-generation sequencing has the potential to improve diagnostic accuracy, assess heritable cancer risk, and guide treatment selection. Through integrative analyses of tumor and germline variants, as well as identifying mutational signatures that influence therapy response, the clinical utility of cancer genomic profiling is being enhanced. Rapid technological innovation and reduced sequencing costs have enabled the profiling of hundreds of cancer-associated genes as part of routine cancer care.