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Low frequency of TSG101/CC2 gene alterations in invasive human breast cancers
Q Wang1, K Driouch, S Courtois
1Unité d'Oncologie Moléculaire, Unité INSERM U453, Centre Léon Bérard, Lyon, France.
Abstract:
Large intragenic deletions of the TSG101/CC2 gene were recently reported in seven of 15 primary metastatic breast cancers. Although the number of samples was small, this observation suggested that TSG101/CC2 alterations were a major event in breast carcinogenesis. To study the frequency of these deletions in invasive breast cancers we analysed 189 primary invasive breast tumours and 59 breast cancer metastases. We detected intragenic rearrangements in only three samples (two primary tumours and one metastasis). Northern blot analysis of 43 tumours without rearrangements failed to detect any abnormalities. Furthermore, we studied TSG101/CC2 in 11 human breast adenocarcinoma cell lines by Southern blot, RT-PCR and sequencing of the entire coding region of the gene, and detected no abnormalities. These results show that genetic alteration of TSG101/CC2 is a rare event in breast cancer.
Insights
Genetic alterations in the TSG101/CC2 gene, initially suggested as a major event in breast cancer, were found to be rare. Further analysis of primary tumors and metastases confirmed these findings, indicating infrequent genetic changes in this gene during breast carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Previous studies suggested large intragenic deletions of the TSG101/CC2 gene in a subset of primary metastatic breast cancers.
- This initial observation implied TSG101/CC2 alterations could be a significant factor in breast cancer development.
Purpose of the Study:
- To investigate the actual frequency of TSG101/CC2 intragenic deletions in a larger cohort of invasive breast cancers.
- To determine the role of TSG101/CC2 genetic alterations in breast carcinogenesis.
Main Methods:
- Analysis of 189 primary invasive breast tumors and 59 breast cancer metastases for intragenic rearrangements.
- Northern blot analysis on 43 tumors without detectable rearrangements.
- Comprehensive analysis of 11 human breast adenocarcinoma cell lines using Southern blot, RT-PCR, and gene sequencing.
Main Results:
- Intragenic rearrangements of TSG101/CC2 were detected in only three out of 248 analyzed samples (two primary tumors, one metastasis).
- No abnormalities were found in 43 tumors via Northern blot analysis.
- No genetic alterations in TSG101/CC2 were identified in the 11 breast cancer cell lines studied.
Conclusions:
- Genetic alterations of the TSG101/CC2 gene are infrequent events in invasive breast cancer.
- The initial suggestion of TSG101/CC2 alterations being a major event in breast carcinogenesis is not supported by this larger study.