Despite continuous advances in cancer pathology, defining the diagnostic classification of some cancers remains a significant challenge. Examples include dedifferentiated tumours, tumours occurring in clinically unusual scenarios and tumours belonging to rare or recently identified classes. As cancer treatment is organised according to cancer streams, this presents a strong barrier to optimal care.
Standard diagnostic work up of cancer tissues involves histological examination, immunohistochemical staining, FISH and other microscopy-based pathology approaches. However, there is a growing appreciation that the genetic alterations in tumours are also diagnostically informative.
In Victoria, the Cancer Of Low sUrvival and unMet Need (COLUMN) program offers whole genome and transcriptome sequencing (WGTS) of challenging cancers. The pathologist-initiated COLUMN sub study takes advantage of this opportunity to test the utility of WGTS in informing diagnosis of tumours for which the primary site is known but that are difficult to classify. Uniquely, WGTS testing is initiated by pathologists rather than treating clinicians, reflecting the focus on diagnostic utility rather than identification of treatment targets for precision oncology.
An initial cohort of 50 patient samples will be sequenced; 22 have been sequenced to date, of which 5 failed due to poor sample quality or tissue cellularity (78% success rate). Analysis of 17 cases demonstrates that diagnosis was clarified in 11 cases (50%). These cases fall in discernable categories, which we are beginning to identify. Illustrative examples will be presented. In conclusion, WGTS is a promising approach in informing diagnosis of cancers that are difficult to diagnose.