Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples

Martelotto, L. G., Baslan, T., Kendall, J., Geyer, F. C., Burke, K. A., Spraggon, L., Piscuoglio, S., Chadalavada, K., Nanjangud, G., Ng, C. K., Moody, P., D'Italia, S., Rodgers, L., Cox, H., da Cruz Paula, A., Stepansky, A., Schizas, M., Wen, H. Y., King, T. A., Norton, L., Weigelt, B., Hicks, J. B., Reis-Filho, J. S. (March 2017) Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples. Nat Med, 23 (3). pp. 376-385. ISSN 1546-170X (Electronic)1078-8956 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/28165479
DOI: 10.1038/nm.4279

Abstract

A substantial proportion of tumors consist of genotypically distinct subpopulations of cancer cells. This intratumor genetic heterogeneity poses a substantial challenge for the implementation of precision medicine. Single-cell genomics constitutes a powerful approach to resolve complex mixtures of cancer cells by tracing cell lineages and discovering cryptic genetic variations that would otherwise be obscured in tumor bulk analyses. Because of the chemical alterations that result from formalin fixation, single-cell genomic approaches have largely remained limited to fresh or rapidly frozen specimens. Here we describe the development and validation of a robust and accurate methodology to perform whole-genome copy-number profiling of single nuclei obtained from formalin-fixed paraffin-embedded clinical tumor samples. We applied the single-cell sequencing approach described here to study the progression from in situ to invasive breast cancer, which revealed that ductal carcinomas in situ show intratumor genetic heterogeneity at diagnosis and that these lesions may progress to invasive breast cancer through a variety of evolutionary processes.

Item Type: Paper
Subjects: bioinformatics
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL labs > Hicks lab
CSHL labs > Wigler lab
Depositing User: Matt Covey
Date: March 2017
Date Deposited: 13 Feb 2017 21:29
Last Modified: 24 Mar 2017 19:01
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34055

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