Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution

Zhou, Wenjing; Muggerud, Aslaug A.; Vu, Phuong; Due, Eldri U.; Sørlie, Therese; Børresen-Dale, Anne-Lise; Wärnberg, Fredrik; Langerød, Anita

doi:10.1016/j.molonc.2009.03.001

« Previous Next »Molecular Oncology
Volume 3, Issue 3 , Pages 214-219, June 2009

Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution

Wenjing Zhou
- Department of Surgical Sciences, Uppsala University, Uppsala SE 75105, Sweden
- These two authors contributed equally to this work.
Aslaug A. Muggerud
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
- Faculty of Medicine, Division The Norwegian Radium Hospital, University of Oslo, 0316 Oslo, Norway
- These two authors contributed equally to this work.
Phuong Vu
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
Eldri U. Due
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
Therese Sørlie
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
- Biomedical Research Group, Department of Bioinformatics, University of Oslo, 0316 Oslo, Norway
Anne-Lise Børresen-Dale
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
- Faculty of Medicine, Division The Norwegian Radium Hospital, University of Oslo, 0316 Oslo, Norway
Fredrik Wärnberg
- Department of Surgical Sciences, Uppsala University, Uppsala SE 75105, Sweden
Anita Langerød
- Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
- Corresponding author. Tel.: +47 22934424.

Received 3 February 2009; accepted 23 March 2009. published online 17 April 2009.

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.