Abstract IA14: Single-cell sequencing in cancer genomics

Abstract

Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming multiple hurdles. This talk will present a collaborative research program that has generated an integrated process to isolate, qualify, and sequence whole exomes of CTCs with high fidelity, using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs.

We validated our process in two prostate cancer patients including one for whom we sequenced CTCs, a lymph node metastasis, and nine cores of the primary tumor. 51 of 73 CTC mutations (70%) were observed in matched tissue. Moreover, we identified 10 early-trunk and 56 metastatic-trunk mutations in the non-CTC tumor samples and found 90% and 73% of these, respectively, in CTC exomes.

The talk will also present some technical considerations for enabling single-cell sequencing of tumor cells, including a description of statistical methods to quantitatively assess the amplification bias resulting from whole-genome amplification of single-cell genomic DNA.

This study establishes a foundation for CTC genomics in the clinic, and initial applications to patient monitoring will be described.

Citation Format: J. Christopher Love. Single-cell sequencing in cancer genomics. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA14.