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

Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008537	RNA-seq dataset of high-grade serous ovarian cancer (HGSC) tumours from long-term survivors performed as part of the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) study. The dataset includes fastq files from 56 HGSC tumours (53 primary tumours and 3 recurrent tumours) from 53 long-term survivor patients. Libraries were generated using the Illumina Stranded mRNA Prep and 150 bp paired-end sequencing was performed to a minimum of 100 million reads on Illumina NovaSeq 6000 instruments.	Illumina NovaSeq 6000	56
EGAD00001009398	Whole-genome sequencing of high-grade serous ovarian cancer (HGSC) tumours and matched normals from long-term survivors performed as part of the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) study. The dataset includes fastq files from 58 HGSC tumours (53 primary tumours and 5 recurrent tumours) and 53 matched normals from 53 long-term survivor patients. Sequence libraries were generated from tumour and matched normal genomic DNA using the KAPA HyperPrep PCR-free library preparation kit (Roche) according to manufacturer’s instructions. Sequencing was carried out by the Kinghorn Centre for Clinical Genomics Sequencing Laboratory (Sydney, Australia) on the HiSeq X Ten System (Illumina) to a minimum base coverage of 30-fold for normal DNA and 60-fold for tumour DNA samples.	HiSeq X Ten	111
EGAD00010002359	Tumor and matched normal DNA profiling by SNP array	Illumina Infinium OmniExpress-24 BeadChip array	111

Publications	Citations
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. Nat Genet 54: 2022 1853-1864	32
Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma. Saner FAM, Takahashi K, Budden T, Pandey A, Ariyaratne D, Zwimpfer TA, Meagher NS, Fereday S, Twomey L, Pishas KI, Hoang T, Bolithon A, Traficante N, Australian Ovarian Cancer Study Group, Alsop K, Christie EL, Kang EY, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Alsop J, Beckmann MW, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, El-Bahrawy MA, Elishaev E, Erber R, Gayther SA, Gentry-Maharaj A, Gilks CB, Harnett PR, Harris HR, Hartmann A, Hein A, Hendley J, Hernandez BY, Jakubowska A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Kluz T, Koziak JM, Kristjansdottir B, Le ND, Lener M, Lester J, Lubiński J, Mateoiu C, Orsulic S, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Soong TR, Steed H, Sukumvanich P, Talhouk A, Taylor SE, Vierkant RA, Wang C, Widschwendter M, Wilkens LR, Winham SJ, Anglesio MS, Berchuck A, Brenton JD, Campbell I, Cook LS, Doherty JA, Fasching PA, Fortner RT, Goodman MT, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sundfeldt K, Swerdlow AJ, Goode EL, DeFazio A, Köbel M, Ramus SJ, Bowtell DDL, Garsed DW. Clin Cancer Res 30: 2024 3481-3498	1

Publications

Citations

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. Nat Genet 54: 2022 1853-1864

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.
Saner FAM, Takahashi K, Budden T, Pandey A, Ariyaratne D, Zwimpfer TA, Meagher NS, Fereday S, Twomey L, Pishas KI, Hoang T, Bolithon A, Traficante N, Australian Ovarian Cancer Study Group, Alsop K, Christie EL, Kang EY, Nelson GS, Ghatage P, Lee CH, Riggan MJ, Alsop J, Beckmann MW, Boros J, Brand AH, Brooks-Wilson A, Carney ME, Coulson P, Courtney-Brooks M, Cushing-Haugen KL, Cybulski C, El-Bahrawy MA, Elishaev E, Erber R, Gayther SA, Gentry-Maharaj A, Gilks CB, Harnett PR, Harris HR, Hartmann A, Hein A, Hendley J, Hernandez BY, Jakubowska A, Jimenez-Linan M, Jones ME, Kaufmann SH, Kennedy CJ, Kluz T, Koziak JM, Kristjansdottir B, Le ND, Lener M, Lester J, Lubiński J, Mateoiu C, Orsulic S, Ruebner M, Schoemaker MJ, Shah M, Sharma R, Sherman ME, Shvetsov YB, Soong TR, Steed H, Sukumvanich P, Talhouk A, Taylor SE, Vierkant RA, Wang C, Widschwendter M, Wilkens LR, Winham SJ, Anglesio MS, Berchuck A, Brenton JD, Campbell I, Cook LS, Doherty JA, Fasching PA, Fortner RT, Goodman MT, Gronwald J, Huntsman DG, Karlan BY, Kelemen LE, Menon U, Modugno F, Pharoah PDP, Schildkraut JM, Sundfeldt K, Swerdlow AJ, Goode EL, DeFazio A, Köbel M, Ramus SJ, Bowtell DDL, Garsed DW. Clin Cancer Res 30: 2024 3481-3498