Molecular profiling and characterization of mutations in cancer tissue have increasingly become a standard of care. Next-generation sequencing technologies facilitate the accurate detection of genetic variants, yet the process of analyzing and classifying more complex alterations remains challenging and time-consuming. Cancer samples are often a mix of different types of cells from the tumor microenvironment; clinical intervention prior to tissue collection may lead to a non-ideal quality sample being used for sequencing. Also, the multitude of clonal populations of cells present in a somatic tumor affects the variant allele frequency of the variant of interest. To identify and interpret complex variants, users often require more insight and in-depth understanding of the processes involved. Sometimes, interpreting these complex variants also requires recognition of the sequencing chemistry and the type of sequencer used.
This whitepaper from PierianDx discusses considerations for interpreting and reporting five different types of complex genetic variants in the context of somatic cancer: co-occurring variants, exon-skipping splice variants, gene fusions, copy number variants, and tumor mutation burden, and microsatellite instability.