The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

Garsed, DW; Pandey, A; Fereday, S; Kennedy, CJ; Takahashi, K; Alsop, K; Hamilton, PT; Hendley, J; Chiew, YE; Traficante, N; Provan, P; Ariyaratne, D; Au-Yeung, G; Bateman, NW; Bowes, L; Brand, A; Christie, EL; Cunningham, JM; Friedlander, M; Grout, B; Harnett, P; Hung, J; McCauley, B; McNally, O; Piskorz, AM; Saner, FAM; Vierkant, RA; Wang, C; Winham, SJ; Pharoah, PDP; Brenton, JD; Conrads, TP; Maxwell, GL; Ramus, SJ; Pearce, CL; Pike, MC; Nelson, BH; Goode, EL; DeFazio, A; Bowtell, DDL

Author(s): Garsed, DW; Pandey, A; Fereday, S; Kennedy, CJ; Takahashi, K; Alsop, K; Hamilton, PT; Hendley, J; Chiew, YE; Traficante, N; Provan, P; Ariyaratne, D; Au-Yeung, G; Bateman, NW; Bowes, L; Brand, A; Christie, EL; Cunningham, JM; Friedlander, M; Grout, B; Harnett, P; Hung, J; McCauley, B; McNally, O; Piskorz, AM; Saner, FAM; Vierkant, RA; Wang, C; Winham, SJ; Pharoah, PDP; Brenton, JD; Conrads, TP; Maxwell, GL; Ramus, SJ; Pearce, CL; Pike, MC; Nelson, BH; Goode, EL; DeFazio, A; Bowtell, DDL;
Details: Publication Year 2022-12,Volume 54,Issue #12,Page 1853-1864
Journal Title: Nature Genetics
Publication Type: Research article
Abstract: Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes and differential immune responses appear to contribute to long-term survival in HGSC.
Keywords: Female; Humans; *Genomics; Survivors; *Ovarian Neoplasms/genetics
Department(s): Laboratory Research; Medical Oncology
PubMed ID: 36456881
Publisher's Version: https://doi.org/10.1038/s41588-022-01230-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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