Extended gene panels identify rare but potentially targetable mutations; initial experience at douglass hanly moir pathology

Currently, oncologists, or even patients themselves, can request extended genetic testing for any solid tumour as a means of identifying potential therapeutic targets. The Full FIND IT panel and FoundationOne CDx are two such extended gene panels that use next generation sequencing to identify genetic aberrations in 33 or 324 actionable cancer-associated genes respectively. FoundationOne also provides information on the tumour mutational burden (TMB). We have identified 17 cases processed at Douglass Hanly Moir Pathology Sydney that have utilised either of these tests since May 2018. Our preliminary Results from 13 cases (results pending for 4) are from patients aged 37 to 78 years, and highlight several rare but well characterised driver mutations (e.g., MSH6 in prostate, CTNNB1 and ARID1A in lung, MET in kidney, TERT promoter and CTNNA1 in bladder), targetable mutations (e.g., MET in lung adenocarcinoma, PTEN loss in prostate adenocarcinoma), and a lung adenocarcinoma with intermediate TMB that may benefit from immunotherapy. Our analysis also shows a high frequency of co-occurring mutations (with TP53 co-occurring the most), that may indicate modifiers of treatment response. Although our series is limited it adds to our understanding of tumour biology and highlights the potential therapeutic utility of extended gene testing.