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1: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14275-80. Epub 2003 Nov 12.
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A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes.

Ley TJ, Minx PJ, Walter MJ, Ries RE, Sun H, McLellan M, DiPersio JF, Link DC, Tomasson MH, Graubert TA, McLeod H, Khoury H, Watson M, Shannon W, Trinkaus K, Heath S, Vardiman JW, Caligiuri MA, Bloomfield CD, Milbrandt JD, Mardis ER, Wilson RK.

Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. tley@im.wustl.edu

In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing approximately 7 million base pairs of DNA from 140 AML samples and 48 controls. We identified six previously described, and seven previously undescribed sequence changes that may be relevant for AML pathogenesis. Because the sequencing templates were generated from primary AML cells, the technique favors the detection of mutations from the most dominant clones within the tumor cell mixture. This strategy represents a viable approach for the detection of potentially relevant, nonrandom mutations in primary human cancer cell genomes.

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PMID: 14614138 [PubMed - indexed for MEDLINE]

PMCID: PMC283582