Dicer, Drosha, and outcomes in patients with ovarian cancer

William M. Merritt, Yvonne G. Lin, Liz Y. Han, Aparna A. Kamat, Whitney A. Spannuth, Rosemarie Schmandt, Diana Urbauer, Len A. Pennacchio, Jan Fang Cheng, Alpa M. Nick, Michael T. Deavers, Alexandra Mourad-Zeidan, Hua Wang, Peter Mueller, Marc E. Lenburg, Joe Gray, Samuel Mok, Michael J. Birrer, Gabriel Lopez-Berestein, Robert L. ColemanMenashe Bar-Eli, Anil K. Sood

Research output: Contribution to journalArticle

523 Citations (Scopus)

Abstract

BACKGROUND: We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer. METHODS: We measured messenger RNA (mRNA) levels of Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111 patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction assay, and compared the results with clinical outcomes. Validation was performed with the use of published microarray data from cohorts of patients with ovarian, breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer-dependent functional assays were performed by means of in vitro transfection with small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS: Levels of Dicer and Drosha mRNA correlated with the levels of expression of the corresponding protein and were decreased in 60% and 51% of ovarian-cancer specimens, respectively. Low Dicer expression was significantly associated with advanced tumor stage (P = 0.007), and low Drosha expression with suboptimal surgical cytoreduction (P = 0.02). Cancer specimens with both high Dicer expression and high Drosha expression were associated with increased median survival (>11 years, vs. 2.66 years for other subgroups; P

Original languageEnglish (US)
Pages (from-to)2641-2650
Number of pages10
JournalNew England Journal of Medicine
Volume359
Issue number25
DOIs
StatePublished - Dec 18 2008
Externally publishedYes

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Ovarian Neoplasms
Small Interfering RNA
DNA Mutational Analysis
Messenger RNA
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Lung Neoplasms
Neoplasms
Breast Neoplasms
Survival
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Merritt, W. M., Lin, Y. G., Han, L. Y., Kamat, A. A., Spannuth, W. A., Schmandt, R., ... Sood, A. K. (2008). Dicer, Drosha, and outcomes in patients with ovarian cancer. New England Journal of Medicine, 359(25), 2641-2650. https://doi.org/10.1056/NEJMoa0803785

Dicer, Drosha, and outcomes in patients with ovarian cancer. / Merritt, William M.; Lin, Yvonne G.; Han, Liz Y.; Kamat, Aparna A.; Spannuth, Whitney A.; Schmandt, Rosemarie; Urbauer, Diana; Pennacchio, Len A.; Cheng, Jan Fang; Nick, Alpa M.; Deavers, Michael T.; Mourad-Zeidan, Alexandra; Wang, Hua; Mueller, Peter; Lenburg, Marc E.; Gray, Joe; Mok, Samuel; Birrer, Michael J.; Lopez-Berestein, Gabriel; Coleman, Robert L.; Bar-Eli, Menashe; Sood, Anil K.

In: New England Journal of Medicine, Vol. 359, No. 25, 18.12.2008, p. 2641-2650.

Research output: Contribution to journalArticle

Merritt, WM, Lin, YG, Han, LY, Kamat, AA, Spannuth, WA, Schmandt, R, Urbauer, D, Pennacchio, LA, Cheng, JF, Nick, AM, Deavers, MT, Mourad-Zeidan, A, Wang, H, Mueller, P, Lenburg, ME, Gray, J, Mok, S, Birrer, MJ, Lopez-Berestein, G, Coleman, RL, Bar-Eli, M & Sood, AK 2008, 'Dicer, Drosha, and outcomes in patients with ovarian cancer', New England Journal of Medicine, vol. 359, no. 25, pp. 2641-2650. https://doi.org/10.1056/NEJMoa0803785
Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. New England Journal of Medicine. 2008 Dec 18;359(25):2641-2650. https://doi.org/10.1056/NEJMoa0803785
Merritt, William M. ; Lin, Yvonne G. ; Han, Liz Y. ; Kamat, Aparna A. ; Spannuth, Whitney A. ; Schmandt, Rosemarie ; Urbauer, Diana ; Pennacchio, Len A. ; Cheng, Jan Fang ; Nick, Alpa M. ; Deavers, Michael T. ; Mourad-Zeidan, Alexandra ; Wang, Hua ; Mueller, Peter ; Lenburg, Marc E. ; Gray, Joe ; Mok, Samuel ; Birrer, Michael J. ; Lopez-Berestein, Gabriel ; Coleman, Robert L. ; Bar-Eli, Menashe ; Sood, Anil K. / Dicer, Drosha, and outcomes in patients with ovarian cancer. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 25. pp. 2641-2650.
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AU - Merritt, William M.

AU - Lin, Yvonne G.

AU - Han, Liz Y.

AU - Kamat, Aparna A.

AU - Spannuth, Whitney A.

AU - Schmandt, Rosemarie

AU - Urbauer, Diana

AU - Pennacchio, Len A.

AU - Cheng, Jan Fang

AU - Nick, Alpa M.

AU - Deavers, Michael T.

AU - Mourad-Zeidan, Alexandra

AU - Wang, Hua

AU - Mueller, Peter

AU - Lenburg, Marc E.

AU - Gray, Joe

AU - Mok, Samuel

AU - Birrer, Michael J.

AU - Lopez-Berestein, Gabriel

AU - Coleman, Robert L.

AU - Bar-Eli, Menashe

AU - Sood, Anil K.

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N2 - BACKGROUND: We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer. METHODS: We measured messenger RNA (mRNA) levels of Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111 patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction assay, and compared the results with clinical outcomes. Validation was performed with the use of published microarray data from cohorts of patients with ovarian, breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer-dependent functional assays were performed by means of in vitro transfection with small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS: Levels of Dicer and Drosha mRNA correlated with the levels of expression of the corresponding protein and were decreased in 60% and 51% of ovarian-cancer specimens, respectively. Low Dicer expression was significantly associated with advanced tumor stage (P = 0.007), and low Drosha expression with suboptimal surgical cytoreduction (P = 0.02). Cancer specimens with both high Dicer expression and high Drosha expression were associated with increased median survival (>11 years, vs. 2.66 years for other subgroups; P

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