Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution
- PMID: 19403344
- PMCID: PMC5527861
- DOI: 10.1016/j.molonc.2009.03.001
Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution
Abstract
In breast cancer, previous studies have suggested that somatic TP53 mutations are likely to be an early event. However, there are controversies regarding the cellular origin and linear course of breast cancer. The purpose of this study was to investigate tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. The entire coding sequence of TP53 was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive cancer (≤15mm) and mixed lesions (i.e. invasive cancer with an in situ component). Of 118 tumor samples, 19 were found to harbor a TP53 mutation; 5 (15.6%) of the pure DCIS, 4 (10.5%) of the pure invasive cancers and 10 (20.8%) of the mixed lesions. In the mixed lesions, both the invasive and the DCIS components showed the same mutation in all 5 cases where the two components were successfully microdissected. Presence of the same mutation in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes.
References
-
- Aas, T. , Borresen, A.L. , Geisler, S. , Smith-Sorensen, B. , Johnsen, H. , Varhaug, J.E. , Akslen, L.A. , Lonning, P.E. , 1996. Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat. Med.. 2, (7) 811–814. - PubMed
-
- Allred, D.C. , Mohsin, S.K. , Fuqua, S.A. , 2001. Histological and biological evolution of human premalignant breast disease. Endocr. Relat. Cancer. 8, (1) 47–61. - PubMed
-
- Borresen-Dale, A.L. , 2003. TP53 and breast cancer. Hum. Mutat.. 21, (3) 292–300. - PubMed
-
- Borresen, A.L. , Andersen, T.I. , Eyfjord, J.E. , Cornelis, R.S. , Thorlacius, S. , Borg, A. , Johansson, U. , Theillet, C. , Scherneck, S. , Hartman, S. , 1995. TP53 mutations and breast cancer prognosis: particularly poor survival rates for cases with mutations in the zinc-binding domains. Genes Chromosomes Cancer. 14, (1) 71–75. - PubMed
-
- Claus, E.B. , Stowe, M. , Carter, D. , 2001. Breast carcinoma in situ: risk factors and screening patterns. J. Natl. Cancer Inst.. 93, (23) 1811–1817. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous
