A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes

Timothy J. Ley; Patrick J. Minx; Matthew J. Walter; Rhonda E. Ries; Hui Sun; Michael McLellan; John F. DiPersio; Daniel C. Link; Michael H. Tomasson; Timothy A. Graubert; Howard McLeod; Hanna Khoury; Mark Watson; William Shannon; Kathryn Trinkaus; Sharon Heath; James W. Vardiman; Michael A. Caligiuri; Clara D. Bloomfield; Jeffrey D. Milbrandt; Elaine R. Mardis; Richard K. Wilson

doi:10.1073/pnas.2335924100

A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes

Timothy J. Ley, Patrick J. Minx, Matthew J. Walter, Rhonda E. Ries, Hui Sun, Michael McLellan, John F. DiPersio, Daniel C. Link, Michael H. Tomasson, Timothy A. Graubert, Howard McLeod, Hanna Khoury, Mark Watson, William Shannon, Kathryn Trinkaus, Sharon Heath, James W. Vardiman, Michael A. Caligiuri, Clara D. Bloomfield, Jeffrey D. MilbrandtElaine R. Mardis, Richard K. Wilson

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52 Scopus citations

Abstract

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 ≈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.

Original language	English
Pages (from-to)	14275-14280
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	SUPPL. 2
DOIs	https://doi.org/10.1073/pnas.2335924100
State	Published - Nov 25 2003

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Ley, T. J., Minx, P. J., Walter, M. J., Ries, R. E., Sun, H., McLellan, M., DiPersio, J. F., Link, D. C., Tomasson, M. H., Graubert, T. A., McLeod, H., Khoury, H., Watson, M., Shannon, W., Trinkaus, K., Heath, S., Vardiman, J. W., Caligiuri, M. A., Bloomfield, C. D., ... Wilson, R. K. (2003). A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. Proceedings of the National Academy of Sciences of the United States of America, 100(SUPPL. 2), 14275-14280. https://doi.org/10.1073/pnas.2335924100

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title = "A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes",

abstract = "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 ≈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.",

author = "Ley, {Timothy J.} and Minx, {Patrick J.} and Walter, {Matthew J.} and Ries, {Rhonda E.} and Hui Sun and Michael McLellan and DiPersio, {John F.} and Link, {Daniel C.} and Tomasson, {Michael H.} and Graubert, {Timothy A.} and Howard McLeod and Hanna Khoury and Mark Watson and William Shannon and Kathryn Trinkaus and Sharon Heath and Vardiman, {James W.} and Caligiuri, {Michael A.} and Bloomfield, {Clara D.} and Milbrandt, {Jeffrey D.} and Mardis, {Elaine R.} and Wilson, {Richard K.}",

year = "2003",

month = nov,

day = "25",

doi = "10.1073/pnas.2335924100",

language = "English",

volume = "100",

pages = "14275--14280",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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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 2003, 'A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. SUPPL. 2, pp. 14275-14280. https://doi.org/10.1073/pnas.2335924100

A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. / Ley, Timothy J.; Minx, Patrick J.; Walter, Matthew J. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. SUPPL. 2, 25.11.2003, p. 14275-14280.

Research output: Contribution to journal › Article › peer-review

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T1 - A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes

AU - Ley, Timothy J.

AU - Minx, Patrick J.

AU - Walter, Matthew J.

AU - Ries, Rhonda E.

AU - Sun, Hui

AU - McLellan, Michael

AU - DiPersio, John F.

AU - Link, Daniel C.

AU - Tomasson, Michael H.

AU - Graubert, Timothy A.

AU - McLeod, Howard

AU - Khoury, Hanna

AU - Watson, Mark

AU - Shannon, William

AU - Trinkaus, Kathryn

AU - Heath, Sharon

AU - Vardiman, James W.

AU - Caligiuri, Michael A.

AU - Bloomfield, Clara D.

AU - Milbrandt, Jeffrey D.

AU - Mardis, Elaine R.

AU - Wilson, Richard K.

PY - 2003/11/25

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - SUPPL. 2

ER -

A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes

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