PTEN mutation, loss of heterozygosity, promoter methylation and expression in colorectal carcinoma: Two hits on the gene?

Hühns,Maja; Salem,Tareq; Schneider,Björn; Krohn,Mathias; Linnebacher,Michael; Prall,Friedrich

doi:10.3892/or.2014.3097

May-2014 Volume 31 Issue 5

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May-2014 Volume 31 Issue 5

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Article

PTEN mutation, loss of heterozygosity, promoter methylation and expression in colorectal carcinoma: Two hits on the gene?

Authors:
- Maja Hühns
- Tareq Salem
- Björn Schneider
- Mathias Krohn
- Michael Linnebacher
- Friedrich Prall
View Affiliations / Copyright

Affiliations: Institute of Pathology, Rostock University, D-18055 Rostock, Germany, Department of Surgery, Rostock University, D-18055 Rostock, Germany
Pages: 2236-2244
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Published online on: March 19, 2014

https://doi.org/10.3892/or.2014.3097
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Abstract

The phosphatase and tensin homologue (PTEN) gene is considered to be a tumour-suppressor gene in various types of cancer, colorectal carcinoma among them. According to the ‘two-hit’ tumour-suppressor gene concept, inactivation occurs by any combination of the following three pathogenetic processes: mutation, loss of one allele [i.e. loss of heterozygosity (LOH)] or promoter methylation. To determine the frequencies of PTEN tumour-suppressor gene features in colorectal carcinoma, we used DNA from colorectal carcinoma xenografts/primary tumour cell lines (N=22) or neoplastic glands isolated by laser-capture microdissection (N=20). Sequencing exons 1-9 of the gene revealed a total of 8 somatic mutations in 5 tumours (3 with high-degree microsatellite instability). In 1 tumour, a truncating mutation of one allele was combined with two missense mutations of the other allele. Polymorphic microsatellite marker analyses (D10S5412, D10S579 and D10S1765) showed complete loss of one allele (i.e. LOH sensu stricto) in 3 tumours, but combined LOH and mutation was found only once. Promoter methylation, tested by MethyLight technology, was found in only 1 of the tumours, not combined with mutation or LOH. In contrast, by immunohistochemistry (mAb 6H2.1), reduction or even loss of PTEN expression was found in 18 tumours. Taken together, PTEN downregulation is a fairly frequent event in colorectal carcinoma, but this apparently is not usually caused by two hits on the gene.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

PTEN mutation, loss of heterozygosity, promoter methylation and expression in colorectal carcinoma: Two hits on the gene?

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