Gene expression profiles of human breast cancer progression

doi:10.1073/pnas.0931261100

Gene expression profiles of human breast cancer progression

^*Applied Genomics Division, Arcturus, 2715 Loker Avenue West, Carlsbad, CA 92008; ^†Department of Pathology, Harvard Medical School, Molecular Pathology Research Unit, Massachusetts General Hospital, Boston, MA 02129; and ^‡Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02129

Communicated by Joan S. Brugge, Harvard Medical School, Boston, MA (received for review November 9, 2002)

Abstract

Although distinct pathological stages of breast cancer have been described, the molecular differences among these stages are largely unknown. Here, through the combined use of laser capture microdissection and DNA microarrays, we have generated in situ gene expression profiles of the premalignant, preinvasive, and invasive stages of human breast cancer. Our data reveal extensive similarities at the transcriptome level among the distinct stages of progression and suggest that gene expression alterations conferring the potential for invasive growth are already present in the preinvasive stages. In contrast to tumor stage, different tumor grades are associated with distinct gene expression signatures. Furthermore, a subset of genes associated with high tumor grade is quantitatively correlated with the transition from preinvasive to invasive growth.

Footnotes

↵ § To whom correspondence may be addressed. E-mail: dsgroi{at}partners.org or merlander{at}arctur.com.
Abbreviations:

LCM,

laser capture microdissection;

CGH,

comparative genomic hybridization;

QRT-PCR,

quantitative real-time PCR;

ADH,

atypical ductal hyperplasia;

DCIS,

ductal carcinoma in situ;

IDC,

invasive ductal carcinoma;

DIG,

digoxigenin;

aRNA,

amplified RNA