Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses

doi:10.1073/pnas.191502998

Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses

Departments of ^*Adult Oncology and ^††Pediatric Oncology, Dana–Farber Cancer Institute, Harvard Medical School, and ^‖Department of Biostatistics, Harvard School of Public Health, 44 Binney Street, Boston, MA 02115; Departments of ^‡Surgery and ^**Pathology, Brigham and Women's Hospital, HMS, 75 Francis Street, Boston, MA 02115; ^¶Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, 1 Kendall Square, Cambridge, MA 02139; and ^‡‡Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114

Contributed by Eric S. Lander

Abstract

We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients.

Footnotes

↵ † A.B. and J.S. contributed equally to data analysis.
↵ § W.G.R. and D.J.S. contributed invaluable patient material and clinical annotation.
↵ §§ T.R.G. and M.M. codirected the project.
↵ ¶¶ To whom reprint requests may be addressed. E-mail: golub{at}genome.wi.mit.edu (for T.R.G.), dsugarbaker{at}partners.org (for D.J.S.), or matthew_meyerson{at}dfci.harvard.edu (for M.M.).
Abbreviations:

SCLC,

small-cell lung carcinomas;

NSCLC,

non-small-cell lung carcinomas;

CM,

colon metastases;

BAC,

bronchioloalveolar carcinoma