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Gene copy numbers of erbB oncogenes in human pheochromocytoma
Krzysztof Sworczak1, Anna Zaczek, Anna Babinska
1Department of Internal Medicine, Endocrinology and Hemostasis, Faculty of Medicine, Medical University of Gdansk, 80-742 Gdansk, Poland.
Abstract:
ErbB-1, -2, -3 and -4 proteins are growth factor receptors, encoded by the family of respective erbB protooncogenes. These receptor-encoding proto-oncogenes frequently undergo amplification, and less frequently, a deletion, in several human neoplasms. The role of the ErbB family in human endocrine neoplasms, including pheochromocytoma (PHEO), was not extensively tested and not previously established. The expression/overexpression of erbB oncogenes in pheochromocytoma tissue was determined only in a few cases, and to the best of our knowledge, their mutations (amplification or deletion) were not examined in any series of PHEO cases. We, therefore, used a double differential polymerase chain reaction (ddPCR) for determination of the amplification/deletion profiles of erbB-1, -2, -3 and -4 genes in formalin-fixed, paraffin embedded (FFPE) specimens of human PHEOs. We examined the average gene copy number (AGCN) of the genes in 36 samples of pheochromocytomas (2 extra-adrenal and 34 adrenal tumors). We found the mean AGCNs of the oncogenes equal 1.18 for erbB-1 [amplification was found in 11/35 cases (31%) and deletion in 6/35 cases (17%)], 2.00 for erbB-2 [amplification was found in 8/34 cases (24%), no deletion was found], 1.36 for erbB-3 [amplification was found in 4/36 cases (11%) and deletion in 1/36 cases (3%)], and 1.22 for erbB-4 [amplification was found in 5/30 cases (17%) and deletion in 1/30 cases (3%)]. A mutation(s) of any erbB oncogene was found in 25/36 (69%) samples tested. Some abnormalities of the erbB oncogenes showed interesting correlations with one another and with clinical features of the tumors. The frequent occurrence of amplifications and deletions of the erbB oncogenes in human pheochromocytoma implies the importance of the gene family in the development of these tumors.
Insights
This study investigated ErbB gene mutations in pheochromocytoma (PHEO). Amplifications and deletions of ErbB genes were common in PHEO, suggesting their importance in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- ErbB proteins are growth factor receptors encoded by protooncogenes.
- These genes frequently undergo amplification or deletion in various cancers.
- The role of ErbB genes in pheochromocytoma (PHEO) and their mutation status were largely unexamined.
Purpose of the Study:
- To determine the amplification and deletion profiles of ErbB-1, -2, -3, and -4 genes in human PHEO specimens.
- To investigate the frequency and patterns of ErbB gene mutations in PHEO.
- To explore potential correlations between ErbB gene abnormalities and clinical features.
Main Methods:
- Utilized double differential polymerase chain reaction (ddPCR) to analyze gene copy numbers.
- Examined formalin-fixed, paraffin-embedded (FFPE) tissues from 36 PHEO samples.
- Quantified average gene copy number (AGCN) for ErbB-1, -2, -3, and -4.
Main Results:
- Mutations (amplification or deletion) in any ErbB oncogene were found in 69% of the 36 PHEO samples.
- ErbB-1 showed amplification in 31% and deletion in 17%.
- ErbB-2 amplification was observed in 24% of cases, with no deletions found.
- ErbB-3 and ErbB-4 also exhibited amplifications and deletions at lower frequencies.
- Abnormalities in ErbB oncogenes showed correlations with each other and with tumor clinical features.
Conclusions:
- Frequent amplifications and deletions of ErbB oncogenes in PHEO highlight their significant role in tumor development.
- The study establishes the mutation profiles of ErbB genes in PHEO, opening avenues for further research.
- These findings suggest ErbB family genes as potential targets for therapeutic strategies in PHEO.