Quantitative multigene FISH on breast carcinomas identifies der(1;16)(q10;p10) as an early event in luminal A tumors
Abstract
In situ detection of genomic alterations in cancer provides information at the single cell level, making it possible to investigate genomic changes in cells in a tissue context. Such topological information is important when studying intratumor heterogeneity as well as alterations related to different steps in tumor progression. We developed a quantitative multigene fluorescence in situ hybridization (QM FISH) method to detect multiple genomic regions in single cells in complex tissues. As a “proof of principle” we applied the method to breast cancer samples to identify partners in whole arm (WA) translocations. WA gain of chromosome arm 1q and loss of chromosome arm 16q are among the most frequent genomic events in breast cancer. By designing five specific FISH probes based on breakpoint information from comparative genomic hybridization array (aCGH) profiles, we visualized chromosomal translocations in clinical samples at the single cell level. By analyzing aCGH data from 295 patients with breast carcinoma with known molecular subtype, we found concurrent WA gain of 1q and loss of 16q to be more frequent in luminal A tumors compared to other molecular subtypes. QM FISH applied to a subset of samples (n = 26) identified a derivative chromosome der(1;16)(q10;p10), a result of a centromere‐close translocation between chromosome arms 1q and 16p. In addition, we observed that the distribution of cells with the translocation varied from sample to sample, some had a homogenous cell population while others displayed intratumor heterogeneity with cell‐to‐cell variation. Finally, for one tumor with both preinvasive and invasive components, the fraction of cells with translocation was lower and more heterogeneous in the preinvasive tumor cells compared to the cells in the invasive component. © 2014 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 26, 2014
- Source ID
- 10.1002/gcc.22237
Entities
People
- Anders Zetterberg
- Anne‐lise Børresen‐dale
- Bjørn Naume
- Hege G. Russnes
- Inga H. Rye
- James Hicks
- Michael Wigler
- Pär Lundin
- Renathe Fjelldal
- Susanne Månér
Organizations
- Army Research Office
- Cold Spring Harbor Laboratory
- Formas
- Karolinska Institutet
- Norwegian Cancer Society
- Oslo University Hospital
- Swedish Cancer Society
- The Breast Cancer Research Foundation
- University of Oslo