Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

Richard A. Moffitt, Raoud Marayati, Elizabeth L. Flate, Keith E. Volmar, S. Gabriela Herrera Loeza, Katherine A. Hoadley, Naim U. Rashid, Lindsay A. Williams, Samuel C. Eaton, Alexander H. Chung, Jadwiga K. Smyla, Judy M. Anderson, Hong Jin Kim, David J. Bentrem, Mark S. Talamonti, Christine A. Iacobuzio-Donahue, Michael A. Hollingsworth, Jen Jen Yeh

Research output: Contribution to journalArticle

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical.

Original languageEnglish (US)
Pages (from-to)1168-1178
Number of pages11
JournalNature Genetics
Volume47
Issue number10
DOIs
StatePublished - Sep 29 2015
Externally publishedYes

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Microdissection
Adenocarcinoma
Neoplasms
Gene Expression
Urinary Bladder Neoplasms
Breast Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., ... Yeh, J. J. (2015). Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nature Genetics, 47(10), 1168-1178. https://doi.org/10.1038/ng.3398

Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. / Moffitt, Richard A.; Marayati, Raoud; Flate, Elizabeth L.; Volmar, Keith E.; Loeza, S. Gabriela Herrera; Hoadley, Katherine A.; Rashid, Naim U.; Williams, Lindsay A.; Eaton, Samuel C.; Chung, Alexander H.; Smyla, Jadwiga K.; Anderson, Judy M.; Kim, Hong Jin; Bentrem, David J.; Talamonti, Mark S.; Iacobuzio-Donahue, Christine A.; Hollingsworth, Michael A.; Yeh, Jen Jen.

In: Nature Genetics, Vol. 47, No. 10, 29.09.2015, p. 1168-1178.

Research output: Contribution to journalArticle

Moffitt, RA, Marayati, R, Flate, EL, Volmar, KE, Loeza, SGH, Hoadley, KA, Rashid, NU, Williams, LA, Eaton, SC, Chung, AH, Smyla, JK, Anderson, JM, Kim, HJ, Bentrem, DJ, Talamonti, MS, Iacobuzio-Donahue, CA, Hollingsworth, MA & Yeh, JJ 2015, 'Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma', Nature Genetics, vol. 47, no. 10, pp. 1168-1178. https://doi.org/10.1038/ng.3398
Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SGH, Hoadley KA et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nature Genetics. 2015 Sep 29;47(10):1168-1178. https://doi.org/10.1038/ng.3398
Moffitt, Richard A. ; Marayati, Raoud ; Flate, Elizabeth L. ; Volmar, Keith E. ; Loeza, S. Gabriela Herrera ; Hoadley, Katherine A. ; Rashid, Naim U. ; Williams, Lindsay A. ; Eaton, Samuel C. ; Chung, Alexander H. ; Smyla, Jadwiga K. ; Anderson, Judy M. ; Kim, Hong Jin ; Bentrem, David J. ; Talamonti, Mark S. ; Iacobuzio-Donahue, Christine A. ; Hollingsworth, Michael A. ; Yeh, Jen Jen. / Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. In: Nature Genetics. 2015 ; Vol. 47, No. 10. pp. 1168-1178.
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