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

Dale W. Garsed; Ahwan Pandey; Sian Fereday; Catherine J. Kennedy; Kazuaki Takahashi; Kathryn Alsop; Phineas T. Hamilton; Joy Hendley; Yoke Eng Chiew; Nadia Traficante; Pamela Provan; Dinuka Ariyaratne; George Au-Yeung; Nicholas W. Bateman; Leanne Bowes; Alison Brand; Elizabeth L. Christie; Julie M. Cunningham; Michael Friedlander; Bronwyn Grout; Paul Harnett; Jillian Hung; Bryan McCauley; Orla McNally; Anna M. Piskorz; Flurina A.M. Saner; Robert A. Vierkant; Chen Wang; Stacey J. Winham; Paul D.P. Pharoah; James D. Brenton; Thomas P. Conrads; George L. Maxwell; Susan J. Ramus; Celeste Leigh Pearce; Malcolm C. Pike; Brad H. Nelson; Ellen L. Goode; Anna DeFazio; David D.L. Bowtell

doi:10.1038/s41588-022-01230-9

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

Dale W. Garsed^*, Ahwan Pandey, Sian Fereday, Catherine J. Kennedy, Kazuaki Takahashi, Kathryn Alsop, Phineas T. Hamilton, Joy Hendley, Yoke Eng Chiew, Nadia Traficante, Pamela Provan, Dinuka Ariyaratne, George Au-Yeung, Nicholas W. Bateman, Leanne Bowes, Alison Brand, Elizabeth L. Christie, Julie M. Cunningham, Michael Friedlander, Bronwyn GroutPaul Harnett, Jillian Hung, Bryan McCauley, Orla McNally, Anna M. Piskorz, Flurina A.M. Saner, Robert A. Vierkant, Chen Wang, Stacey J. Winham, Paul D.P. Pharoah, James D. Brenton, Thomas P. Conrads, George L. Maxwell, Susan J. Ramus, Celeste Leigh Pearce, Malcolm C. Pike, Brad H. Nelson, Ellen L. Goode, Anna DeFazio, David D.L. Bowtell^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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.

Original language	English
Pages (from-to)	1853-1864
Number of pages	12
Journal	Nature Genetics
Volume	54
Issue number	12
DOIs	https://doi.org/10.1038/s41588-022-01230-9
State	Published - Dec 2022
Externally published	Yes

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Garsed, D. W., Pandey, A., Fereday, S., Kennedy, C. J., Takahashi, K., Alsop, K., Hamilton, P. T., Hendley, J., Chiew, Y. E., Traficante, N., Provan, P., Ariyaratne, D., Au-Yeung, G., Bateman, N. W., Bowes, L., Brand, A., Christie, E. L., Cunningham, J. M., Friedlander, M., ... Bowtell, D. D. L. (2022). The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer. Nature Genetics, 54(12), 1853-1864. https://doi.org/10.1038/s41588-022-01230-9

@article{426925716b3c4569bf4f4b28632bc491,

title = "The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer",

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.",

author = "Garsed, {Dale W.} and Ahwan Pandey and Sian Fereday and Kennedy, {Catherine J.} and Kazuaki Takahashi and Kathryn Alsop and Hamilton, {Phineas T.} and Joy Hendley and Chiew, {Yoke Eng} and Nadia Traficante and Pamela Provan and Dinuka Ariyaratne and George Au-Yeung and Bateman, {Nicholas W.} and Leanne Bowes and Alison Brand and Christie, {Elizabeth L.} and Cunningham, {Julie M.} and Michael Friedlander and Bronwyn Grout and Paul Harnett and Jillian Hung and Bryan McCauley and Orla McNally and Piskorz, {Anna M.} and Saner, {Flurina A.M.} and Vierkant, {Robert A.} and Chen Wang and Winham, {Stacey J.} and Pharoah, {Paul D.P.} and Brenton, {James D.} and Conrads, {Thomas P.} and Maxwell, {George L.} and Ramus, {Susan J.} and Pearce, {Celeste Leigh} and Pike, {Malcolm C.} and Nelson, {Brad H.} and Goode, {Ellen L.} and Anna DeFazio and Bowtell, {David D.L.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

month = dec,

doi = "10.1038/s41588-022-01230-9",

language = "English",

volume = "54",

pages = "1853--1864",

journal = "Nature Genetics",

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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 2022, 'The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer', Nature Genetics, vol. 54, no. 12, pp. 1853-1864. https://doi.org/10.1038/s41588-022-01230-9

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T1 - The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

AU - Garsed, Dale W.

AU - Pandey, Ahwan

AU - Fereday, Sian

AU - Kennedy, Catherine J.

AU - Takahashi, Kazuaki

AU - Alsop, Kathryn

AU - Hamilton, Phineas T.

AU - Hendley, Joy

AU - Chiew, Yoke Eng

AU - Traficante, Nadia

AU - Provan, Pamela

AU - Ariyaratne, Dinuka

AU - Au-Yeung, George

AU - Bateman, Nicholas W.

AU - Bowes, Leanne

AU - Brand, Alison

AU - Christie, Elizabeth L.

AU - Cunningham, Julie M.

AU - Friedlander, Michael

AU - Grout, Bronwyn

AU - Harnett, Paul

AU - Hung, Jillian

AU - McCauley, Bryan

AU - McNally, Orla

AU - Piskorz, Anna M.

AU - Saner, Flurina A.M.

AU - Vierkant, Robert A.

AU - Wang, Chen

AU - Winham, Stacey J.

AU - Pharoah, Paul D.P.

AU - Brenton, James D.

AU - Conrads, Thomas P.

AU - Maxwell, George L.

AU - Ramus, Susan J.

AU - Pearce, Celeste Leigh

AU - Pike, Malcolm C.

AU - Nelson, Brad H.

AU - Goode, Ellen L.

AU - DeFazio, Anna

AU - Bowtell, David D.L.

PY - 2022/12

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N2 - 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.

AB - 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.

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JF - Nature Genetics

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ER -

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

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