E-Poster Presentation 34th Lorne Cancer Conference 2022

Whole Genome Sequencing of rare gynaecological cancers  (#322)

Ratana Lim 1 , Amandine Carmagnac 1 , Cassandra Vandenberg 1 2 , Genevieve Dall 1 2 , Kristy Shield-Artin 1 2 , Gayanie Ratnayake 3 , Warren Zhou 1 , Orla McNally 3 4 , Justin Bedo 1 2 , Jocelyn Penington 1 , Kym Pham Stewart 2 , Layla Zhu 2 , Oliver Hofmann 2 , Joseph Vissers 2 4 , Sean Grimmond 2 , Matthew Wakefield 1 2 , Damien Kee 1 4 , Tony Papenfuss 1 2 4 , Holly Barker 1 2 , Clare L Scott 1 2 3 4
  1. WEHI, Parkville, Victoria, Australia
  2. The University of Melbourne, Parkville, Victoria, Australia
  3. The Royal Women's Hospital, Parkville, Victoria, Australia
  4. The Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Collectively, rare cancers (RC) account for 22% of all cancer diagnoses but 30% of cancer deaths, being associated with poorer outcomes and limited evidence-based treatment. We designed the national WEHI-Stafford Fox Rare Cancer Program (SFRCP) to enable RC research through streamlined laboratory sample processing, allowing for generation of peripheral blood mononuclear cells (PBMCs), DNA, and RNA, as well as next-generation sequencing (NGS).

 

475 RC patients have been accrued nationally. We perform various methods of NGS depending on tumour sample quality. This included Whole Genome Sequencing (WGS) on 126 samples, of which 107 (97 fresh frozen, 10 FFPE) were rare gynaecological cancers (RGC). H&E tissue sections from biopsies or surgical resections were reviewed by our anatomical pathologist for morphology, diagnosis confirmation and to estimate tumour purity.

 

Of 107 RGC, 96 cases resulted in successful WGS. Actionable aberrations were detected in 70/96 cases (72.9%). Fifty aberrations were highly actionable (52.0%) indicating potential patient benefit from four main drug classes: PARP inhibitor therapy (eg homologous recombination deficiency (HRD) due to BRCA1/2 mutations or Cosmic mutational signature 3) in 17/96 cases (17.7%); RAF dimer+MEK inhibition in 19/96 cases (19.8%); immune checkpoint inhibitor therapy (high tumour mutational burden (TMB), over 15 mutations/megabase DNA) in 7/96 cases (7.3%); and HER2 targeted therapy (amplification or mutation of ERBB2) in 5/96 cases (5.2%). Additional moderate impact aberrations, such as CCNE1 amplifications, ARID1A, AKT and PIK3CA mutations were also observed frequently.

 

Actionable aberrations were detected in 72.9% of cases across many different RGC types. Whilst not all patients were able to access treatment, we strive to improve access to earlier testing where the patient is well enough to receive treatment, including on a clinical trial. Access to umbrella trials of a wider variety of therapeutic compounds, including by tele-trials, is important, as patients with RC deserve the best possible therapeutic guidance.