Back to Search
Start Over
Temporal dissection of tumorigenesis in primary cancers
- Source :
- 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 T, 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 2011, ' Temporal dissection of tumorigenesis in primary cancers ', Cancer Drug Discovery and Development, vol. 1, no. 2, pp. 137-143 . https://doi.org/10.1158/2159-8290.CD-11-0028
- Publication Year :
- 2011
-
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
- Subjects :
- Senescence
Mutagenesis (molecular biology technique)
Disease
Biology
medicine.disease_cause
Bioinformatics
DNA sequencing
Article
medicine
Humans
Chromosome Aberrations
Ovarian Neoplasms
Mutation
Cancer
Oncogenes
medicine.disease
Cystadenocarcinoma, Serous
Serous fluid
Cell Transformation, Neoplastic
Oncology
Carcinoma, Squamous Cell
Disease Progression
Female
Tumor Suppressor Protein p53
Carcinogenesis
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 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 T, 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 2011, ' Temporal dissection of tumorigenesis in primary cancers ', Cancer Drug Discovery and Development, vol. 1, no. 2, pp. 137-143 . https://doi.org/10.1158/2159-8290.CD-11-0028
- Accession number :
- edsair.doi.dedup.....966696cda502a42c25b2a9edd6106fd8