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Cited by 266

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Temporal Dissection of Tumorigenesis in Primary Cancers

Open access
Durinck, Steffen, Ho, Christine, Wang, Nicholas J., Liao, Wilson, Jakkula, Lakshmi R., Collisson, Eric A., Pons, Jennifer, Chan, Sai-Wing, Lam, Ernest T., Chu, Catherine, Park, Kyunghee, Hong, Sung-woo, Hur, Joe S., Huh, Nam, Neuhaus, Isaac M., Yu, Siegrid S., Grekin, Roy C., Mauro, Theodora M., Cleaver, James E., Kwok, Pui-Yan, LeBoit, Philip E., Getz, Gad, Cibulskis, Kristian, Aster, Jon C., Huang, Haiyan, Purdom, Elizabeth, Li, Jian, Bolund, Lars, Arron, Sarah T., Gray, Joe W., Spellman, Paul T., Cho, Raymond J.·2011·Cancer Discovery

Abstract

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes. Significance: Our approach reveals sequential ordering of oncogenic events in individual cancers, based on chromosomal rearrangements. Identifying the earliest abnormalities in cancer represents a critical step in timely diagnosis and deployment of targeted therapeutics. Cancer Discovery; 1(2); 137–43. © 2011 AACR. This article is highlighted in the In This Issue feature, p. 91

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Metadata

Authors
Durinck, S., Ho, C., Wang, N. J., Liao, W., Jakkula, L. R., Collisson, E. A., Pons, J., Chan, S.-W., Lam, E. T., Chu, C., Park, K., Hong, S.-W., Hur, J. S., Huh, N., Neuhaus, I. M., Yu, S. S., Grekin, R. C., Mauro, T. M., Cleaver, J. E., Kwok, P.-Y., LeBoit, P. E., Getz, G., Cibulskis, K., Aster, J. C., Huang, H., Purdom, E., Li, J., Bolund, L., Arron, S. T., Gray, J. W., Spellman, P. T., & Cho, R. J.
Venue
Cancer Discovery
Published
2011-07-01
Volume
1
Issue
2
Pages
137-143
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
OpenAlex
W2128537223
Cited by
266
References
6
FWCI
7.95
Type
journal article
Language
en
Open access
bronze

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