Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma

Genomic scar signatures associated with homologous recombination deficiency predict adverse... We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC spec- imens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Medicine Springer Journals

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Biomedicine; Molecular Medicine; Human Genetics; Internal Medicine
ISSN
0946-2716
eISSN
1432-1440
D.O.I.
10.1007/s00109-018-1643-8
Publisher site
See Article on Publisher Site

Abstract

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC spec- imens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified

Journal

Journal of Molecular Medicine – Springer Journals

Published: May 3, 2018

References

  • Clear cell carcinoma of the ovary: a review of the literature
    Carmen, MG; Birrer, M; Schorge, JO
  • Clear-cell carcinoma of the ovary
    Fujiwara, K; Shintani, D; Nishikawa, T
  • Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers
    Chan, JK; Teoh, D; Hu, JM; Shin, JY; Osann, K; Kapp, DS
  • Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy
    Sugiyama, T; Kamura, T; Kigawa, J; Terakawa, N; Kikuchi, Y; Kita, T; Suzuki, M; Sato, I; Taguchi, K
  • Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising
    Jekimovs, C; Bolderson, E; Suraweera, A; Adams, M; O’Byrne, KJ; Richard, DJ
  • Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer
    Telli, ML; Timms, KM; Reid, J; Hennessy, B; Mills, GB; Jensen, KC; Szallasi, Z; Barry, WT; Winer, EP; Tung, NM; Isakoff, SJ; Ryan, PD; Greene-Colozzi, A; Gutin, A; Sangale, Z; Iliev, D; Neff, C; Abkevich, V; Jones, JT; Lanchbury, JS; Hartman, AR; Garber, JE; Ford, JM; Silver, DP; Richardson, AL
  • BRCA1 and BRCA2: different roles in a common pathway of genome protection
    Roy, R; Chun, J; Powell, SN
  • Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer
    Konstantinopoulos, PA; Ceccaldi, R; Shapiro, GI; D'Andrea, AD
  • Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 part 1): an international, multicentre, open-label, phase 2 trial
    Swisher, EM; Lin, KK; Oza, AM; Scott, CL; Giordano, H; Sun, J; Konecny, GE; Coleman, RL; Tinker, AV; O'Malley, DM; Kristeleit, RS; Ma, L; Bell-McGuinn, KM; Brenton, JD; Cragun, JM; Oaknin, A; Ray-Coquard, I; Harrell, MI; Mann, E; Kaufmann, SH; Floquet, A; Leary, A; Harding, TC; Goble, S; Maloney, L; Isaacson, J; Allen, AR; Rolfe, L; Yelensky, R; Raponi, M; McNeish, IA
  • Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: clinical and molecular characterization
    Lheureux, S; Lai, Z; Dougherty, BA; Runswick, S; Hodgson, DR; Timms, KM; Lanchbury, JS; Kaye, S; Gourley, C; Bowtell, D; Kohn, EC; Scott, C; Matulonis, U; Panzarella, T; Karakasis, K; Burnier, JV; Gilks, CB; O'Connor, MJ; Robertson, JD; Ledermann, J; Barrett, JC; Ho, TW; Oza, AM
  • HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
    Davies, H; Glodzik, D; Morganella, S; Yates, LR; Staaf, J; Zou, X; Ramakrishna, M; Martin, S; Boyault, S; Sieuwerts, AM; Simpson, PT; King, TA; Raine, K; Eyfjord, JE; Kong, G; Borg, Å; Birney, E; Stunnenberg, HG; Vijver, MJ; Børresen-Dale, AL; Martens, JWM; Span, PN; Lakhani, SR; Vincent-Salomon, A; Sotiriou, C; Tutt, A; Thompson, AM; van Laere, S; Richardson, AL; Viari, A; Campbell, PJ; Stratton, MR; Nik-Zainal, S
  • Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents
    Birkbak, NJ; Wang, ZC; Kim, JY; Eklund, AC; Li, Q; Tian, R; Bowman-Colin, C; Li, Y; Greene-Colozzi, A; Iglehart, JD; Tung, N; Ryan, PD; Garber, JE; Silver, DP; Szallasi, Z; Richardson, AL
  • Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation
    Popova, T; Manie, E; Rieunier, G; Caux-Moncoutier, V; Tirapo, C; Dubois, T; Delattre, O; Sigal-Zafrani, B; Bollet, M; Longy, M; Houdayer, C; Sastre-Garau, X; Vincent-Salomon, A; Stoppa-Lyonnet, D; Stern, MH
  • Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
    Abkevich, V; Timms, KM; Hennessy, BT; Potter, J; Carey, MS; Meyer, LA; Smith-McCune, K; Broaddus, R; Lu, KH; Chen, J; Tran, TV; Williams, D; Iliev, D; Jammulapati, S; FitzGerald, LM; Krivak, T; DeLoia, JA; Gutin, A; Mills, GB; Lanchbury, JS
  • Phase II study of gemcitabine, carboplatin, and iniparib as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer with assessment of a tumor-based measure of genomic instability: PrECOG 0105
    Telli, ML; Jensen, KC; Vinayak, S; Kurian, AW; Lipson, JA; Flaherty, PJ; Timms, K; Abkevich, V; Schackmann, EA; Wapnir, IL; Carlson, RW; Chang, PJ; Sparano, JA; Head, B; Goldstein, LJ; Haley, B; Dakhil, SR; Reid, JE; Hartman, AR; Manola, J; Ford, JM
  • Pan-cancer analysis of genomic scar signatures associated with homologous recombination deficiency suggests novel indications for existing cancer drugs
    Marquard, AM; Eklund, AC; Joshi, T; Krzystanek, M; Favero, F; Wang, ZC; Richardson, AL; Silver, DP; Szallasi, Z; Birkbak, NJ
  • Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology
    Chao, A; Wu, RC; Jung, SM; Lee, YS; Chen, SJ; Lu, YL; Tsai, CL; Lin, CY; Tang, YH; Chen, MY; Huang, HJ; Chou, HH; Huang, KG; Chang, TC; Wang, TH; Lai, CH
  • Allele-specific copy number analysis of tumors
    Loo, P; Nordgard, SH; Lingjaerde, OC; Russnes, HG; Rye, IH; Sun, W; Weigman, VJ; Marynen, P; Zetterberg, A; Naume, B
  • Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer
    Mirza, MR; Monk, BJ; Herrstedt, J; Oza, AM; Mahner, S; Redondo, A; Fabbro, M; Ledermann, JA; Lorusso, D; Vergote, I; Ben-Baruch, NE; Marth, C; Mądry, R; Christensen, RD; Berek, JS; Dørum, A; Tinker, AV; du Bois, A; González-Martín, A; Follana, P; Benigno, B; Rosenberg, P; Gilbert, L; Rimel, BJ; Buscema, J; Balser, JP; Agarwal, S; Matulonis, UA
  • Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer
    Chao, A; Chang, TC; Lapke, N; Jung, SM; Chi, P; Chen, CH; Yang, LY; Lin, CT; Huang, HJ; Chou, HH; Liou, JD; Chen, SJ; Wang, TH; Lai, CH
  • BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer
    Sakamoto, I; Hirotsu, Y; Nakagomi, H; Ouchi, H; Ikegami, A; Teramoto, K; Amemiya, K; Mochizuki, H; Omata, M

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