Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine

被引：327

作者：

Dias-Santagata, Dora ^{[1
,2
]}

Akhavanfard, Sara ^{[2
,3
]}

David, Serena S. ^{[2
,3
]}

Vernovsky, Kathy ^{[2
,3
]}

Kuhlmann, Georgiana ^{[1
,2
]}

Boisvert, Susan L. ^{[2
,3
]}

Stubbs, Hannah ^{[1
,2
]}

McDermott, Ultan ^{[4
,5
]}

Settleman, Jeffrey ^{[4
,5
]}

Kwak, Eunice L. ^{[2
,3
]}

Clark, Jeffrey W. ^{[2
,3
]}

Isakoff, Steven J. ^{[2
,3
]}

Sequist, Lecia V. ^{[2
,3
]}

Engelman, Jeffrey A. ^{[2
,3
]}

Lynch, Thomas J. ^{[2
,3
]}

Haber, Daniel A. ^{[2
,3
]}

Louis, David N. ^{[1
,2
]}

Ellisen, Leif W. ^{[2
,3
]}

Borger, Darrell R. ^{[2
,3
]}

Lafrate, A. John ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, Charlestown, MA USA

[5] Harvard Univ, Sch Med, Charlestown, MA USA

来源：

EMBO MOLECULAR MEDICINE | 2010年 / 2卷 / 05期

关键词：

cancer; genotyping; profiling; targeted therapies; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; FACTOR RECEPTOR MUTATIONS; SOMATIC MUTATIONS; HUMAN BREAST; EGFR MUTATIONS; GENE FAMILY; GEFITINIB; ADENOCARCINOMA; PATHWAY;

D O I：

10.1002/emmm.201000070

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. we developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management.

引用

页码：146 / 158

页数：13

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