A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

A. C. Berger, A. Korkut, R. S. Kanchi, A. M. Hegde, W. Lenoir, W. Liu, Y. Liu, H. Fan, H. Shen, V. Ravikumar, A. Rao, A. Schultz, X. Li, P. Sumazin, C. Williams, P. Mestdagh, P. H. Gunaratne, C. Yau, R. Bowlby, A. G. RobertsonD. G. Tiezzi, C. Wang, A. D. Cherniack, A. K. Godwin, N. M. Kuderer, J. S. Rader, R. E. Zuna, A. K. Sood, A. J. Lazar, A. I. Ojesina, C. Adebamowo, S. N. Adebamowo, K. A. Baggerly, T. W. Chen, H. S. Chiu, S. Lefever, L. Liu, K. MacKenzie, S. Orsulic, J. Roszik, C. S. Shelley, Q. Song, C. P. Vellano, N. Wentzensen, Cancer Genome Atlas Research Network, J. N. Weinstein, G. B. Mills, D. A. Levine, R. Akbani, Marino Mirella (collaborator)

Research output: Contribution to journalArticle

Abstract

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
Original languageEnglish
Pages (from-to)690-705.e9
JournalCancer Cell
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 9 2018
Externally publishedYes

Fingerprint

Long Noncoding RNA
Breast Neoplasms
Atlases
Neoplasms
Genome
Genes
Decision Trees
Estrogen Receptors
Immunotherapy
Breast
Leukocytes
Therapeutics

Keywords

  • TCGA
  • The Cancer Genome Atlas
  • breast cancer
  • cervical cancer
  • gynecologic cancer
  • omics
  • ovarian cancer
  • pan-gynecologic
  • uterine cancer
  • uterine carcinosarcoma

Cite this

Berger, A. C., Korkut, A., Kanchi, R. S., Hegde, A. M., Lenoir, W., Liu, W., ... (collaborator), M. M. (2018). A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. Cancer Cell, 33(4), 690-705.e9. https://doi.org/10.1016/j.ccell.2018.03.014

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. / Berger, A. C.; Korkut, A.; Kanchi, R. S.; Hegde, A. M.; Lenoir, W.; Liu, W.; Liu, Y.; Fan, H.; Shen, H.; Ravikumar, V.; Rao, A.; Schultz, A.; Li, X.; Sumazin, P.; Williams, C.; Mestdagh, P.; Gunaratne, P. H.; Yau, C.; Bowlby, R.; Robertson, A. G.; Tiezzi, D. G.; Wang, C.; Cherniack, A. D.; Godwin, A. K.; Kuderer, N. M.; Rader, J. S.; Zuna, R. E.; Sood, A. K.; Lazar, A. J.; Ojesina, A. I.; Adebamowo, C.; Adebamowo, S. N.; Baggerly, K. A.; Chen, T. W.; Chiu, H. S.; Lefever, S.; Liu, L.; MacKenzie, K.; Orsulic, S.; Roszik, J.; Shelley, C. S.; Song, Q.; Vellano, C. P.; Wentzensen, N.; Network, Cancer Genome Atlas Research; Weinstein, J. N.; Mills, G. B.; Levine, D. A.; Akbani, R.; (collaborator), Marino Mirella.

In: Cancer Cell, Vol. 33, No. 4, 09.04.2018, p. 690-705.e9.

Research output: Contribution to journalArticle

Berger, AC, Korkut, A, Kanchi, RS, Hegde, AM, Lenoir, W, Liu, W, Liu, Y, Fan, H, Shen, H, Ravikumar, V, Rao, A, Schultz, A, Li, X, Sumazin, P, Williams, C, Mestdagh, P, Gunaratne, PH, Yau, C, Bowlby, R, Robertson, AG, Tiezzi, DG, Wang, C, Cherniack, AD, Godwin, AK, Kuderer, NM, Rader, JS, Zuna, RE, Sood, AK, Lazar, AJ, Ojesina, AI, Adebamowo, C, Adebamowo, SN, Baggerly, KA, Chen, TW, Chiu, HS, Lefever, S, Liu, L, MacKenzie, K, Orsulic, S, Roszik, J, Shelley, CS, Song, Q, Vellano, CP, Wentzensen, N, Network, CGAR, Weinstein, JN, Mills, GB, Levine, DA, Akbani, R & (collaborator), MM 2018, 'A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers', Cancer Cell, vol. 33, no. 4, pp. 690-705.e9. https://doi.org/10.1016/j.ccell.2018.03.014
Berger AC, Korkut A, Kanchi RS, Hegde AM, Lenoir W, Liu W et al. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. Cancer Cell. 2018 Apr 9;33(4):690-705.e9. https://doi.org/10.1016/j.ccell.2018.03.014
Berger, A. C. ; Korkut, A. ; Kanchi, R. S. ; Hegde, A. M. ; Lenoir, W. ; Liu, W. ; Liu, Y. ; Fan, H. ; Shen, H. ; Ravikumar, V. ; Rao, A. ; Schultz, A. ; Li, X. ; Sumazin, P. ; Williams, C. ; Mestdagh, P. ; Gunaratne, P. H. ; Yau, C. ; Bowlby, R. ; Robertson, A. G. ; Tiezzi, D. G. ; Wang, C. ; Cherniack, A. D. ; Godwin, A. K. ; Kuderer, N. M. ; Rader, J. S. ; Zuna, R. E. ; Sood, A. K. ; Lazar, A. J. ; Ojesina, A. I. ; Adebamowo, C. ; Adebamowo, S. N. ; Baggerly, K. A. ; Chen, T. W. ; Chiu, H. S. ; Lefever, S. ; Liu, L. ; MacKenzie, K. ; Orsulic, S. ; Roszik, J. ; Shelley, C. S. ; Song, Q. ; Vellano, C. P. ; Wentzensen, N. ; Network, Cancer Genome Atlas Research ; Weinstein, J. N. ; Mills, G. B. ; Levine, D. A. ; Akbani, R. ; (collaborator), Marino Mirella. / A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. In: Cancer Cell. 2018 ; Vol. 33, No. 4. pp. 690-705.e9.
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T1 - A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

AU - Berger, A. C.

AU - Korkut, A.

AU - Kanchi, R. S.

AU - Hegde, A. M.

AU - Lenoir, W.

AU - Liu, W.

AU - Liu, Y.

AU - Fan, H.

AU - Shen, H.

AU - Ravikumar, V.

AU - Rao, A.

AU - Schultz, A.

AU - Li, X.

AU - Sumazin, P.

AU - Williams, C.

AU - Mestdagh, P.

AU - Gunaratne, P. H.

AU - Yau, C.

AU - Bowlby, R.

AU - Robertson, A. G.

AU - Tiezzi, D. G.

AU - Wang, C.

AU - Cherniack, A. D.

AU - Godwin, A. K.

AU - Kuderer, N. M.

AU - Rader, J. S.

AU - Zuna, R. E.

AU - Sood, A. K.

AU - Lazar, A. J.

AU - Ojesina, A. I.

AU - Adebamowo, C.

AU - Adebamowo, S. N.

AU - Baggerly, K. A.

AU - Chen, T. W.

AU - Chiu, H. S.

AU - Lefever, S.

AU - Liu, L.

AU - MacKenzie, K.

AU - Orsulic, S.

AU - Roszik, J.

AU - Shelley, C. S.

AU - Song, Q.

AU - Vellano, C. P.

AU - Wentzensen, N.

AU - Network, Cancer Genome Atlas Research

AU - Weinstein, J. N.

AU - Mills, G. B.

AU - Levine, D. A.

AU - Akbani, R.

AU - (collaborator), Marino Mirella

N1 - LR: 20180714; CI: Copyright (c) 2018; GR: P30 CA016672/CA/NCI NIH HHS/United States; GR: P30 CA016087/CA/NCI NIH HHS/United States; GR: U24 CA143882/CA/NCI NIH HHS/United States; GR: U54 HG003067/HG/NHGRI NIH HHS/United States; GR: U24 CA143835/CA/NCI NIH HHS/United States; GR: P50 CA217685/CA/NCI NIH HHS/United States; GR: U24 CA143866/CA/NCI NIH HHS/United States; GR: U24 CA210950/CA/NCI NIH HHS/United States; GR: U24 CA143845/CA/NCI NIH HHS/United States; GR: U24 CA143799/CA/NCI NIH HHS/United States; GR: P50 CA098258/CA/NCI NIH HHS/United States; GR: U01 CA168394/CA/NCI NIH HHS/United States; GR: U01 CA217842/CA/NCI NIH HHS/United States; GR: U54 HG003273/HG/NHGRI NIH HHS/United States; GR: U24 CA144025/CA/NCI NIH HHS/United States; GR: U24 CA143840/CA/NCI NIH HHS/United States; GR: U24 CA143843/CA/NCI NIH HHS/United States; GR: U24 CA143858/CA/NCI NIH HHS/United States; GR: U24 CA143848/CA/NCI NIH HHS/United States; GR: U24 CA210957/CA/NCI NIH HHS/United States; GR: U54 HG003079/HG/NHGRI NIH HHS/United States; GR: U24 CA210949/CA/NCI NIH HHS/United States; GR: U24 CA143883/CA/NCI NIH HHS/United States; GR: U24 CA143867/CA/NCI NIH HHS/United States; GR: U24 CA199461/CA/NCI NIH HHS/United States; GR: U24 CA210990/CA/NCI NIH HHS/United States; JID: 101130617; NIHMS958065; OTO: NOTNLM; PMCR: 2019/04/09 00:00; 2017/10/26 00:00 [received]; 2018/02/22 00:00 [revised]; 2018/03/12 00:00 [accepted]; 2019/04/09 00:00 [pmc-release]; 2018/04/07 06:00 [pubmed]; 2018/04/07 06:00 [medline]; 2018/04/07 06:00 [entrez]; ppublish

PY - 2018/4/9

Y1 - 2018/4/9

N2 - We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

AB - We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

KW - TCGA

KW - The Cancer Genome Atlas

KW - breast cancer

KW - cervical cancer

KW - gynecologic cancer

KW - omics

KW - ovarian cancer

KW - pan-gynecologic

KW - uterine cancer

KW - uterine carcinosarcoma

U2 - 10.1016/j.ccell.2018.03.014

DO - 10.1016/j.ccell.2018.03.014

M3 - Article

VL - 33

SP - 690-705.e9

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 4

ER -