Establishment of clinical curation principles for whole genome and transcriptome sequencing of CUP

DR CAMILLA MITCHELL
Curation Scientist
UMCCR

Cancers of Unknown Primary (CUP) is diagnosed when a patient presents with metastatic cancer with no identifiable primary cancer, despite standardised diagnostic investigations. Treatment for metastatic disease is generally based on the primary cancer type. However, CUPs are largely treated with non-targeted empirical chemotherapy, leading to poor survival outcomes.

The SUPER-NEXT study uses whole genome and transcriptome sequencing to interrogate the molecular landscape of CUPs to help resolve likely tissue of origin, a likely cancer diagnosis, find potentially actionable genomic targets, and facilitate access to tumour stream-specific treatment approaches. Through our work of curation and interpretation of whole genome findings, plus integration with histopathological and clinical review, we have identified three main areas of whole genome and transcriptome sequencing curation which can routinely be used to inform cancer diagnosis.

Dr Camilla Mitchell is a curation scientist with the UMCCR. Camilla received her PhD in calcium signalling pathways in developmental neuroscience, from the University of Tasmania in 2014, before switching research streams to cancer cell biology.  She investigated mechanisms of cell invasion in neuroblastoma at the Children’s Hospital at Westmead, and the PI3K signalling pathway in colorectal cancer and PIK3CA-related overgrowth syndromes at Peter MacCallum Cancer Centre.  In 2021, Camilla transitioned from lab-based research, into the role of cancer genome curation scientist, where she focuses on curation of whole genome and transcriptome sequencing of cancers of unknown primary, within the SUPER-NEXT study, to determine which variants are relevant in informing diagnosis, prognosis, and treatment, to inform clinical care.