Microsatellite Instability within the CD30 Gene Promoter Distinguishes between Normal and Neoplastic Cells in Lymphoma
Alexander J. Rea
School of Chemistry and Biochemistry, University of Western Australia, Crawley WA, Australia and Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley WA, Australia. q
Maria Franchina
School of Chemistry and Biochemistry, University of Western Australia, Crawley WA, Australia.
Dominic V Spagnolo
School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia and Path West Laboratory Medicine WA, Perth, Australia.
Daniela Ulgiati
School of Chemistry and Biochemistry, University of Western Australia, Crawley WA, Australia.
Lawrence J. Abraham *
School of Chemistry and Biochemistry, University of Western Australia, Crawley WA, Australia and Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley WA, Australia. q
*Author to whom correspondence should be addressed.
Abstract
Aims: As differences in promoter activity and CD30 surface expression between CD30+ lymphoid cell-lines and peripheral blood leukocytes have been shown previously to be independent of the size of the CD30 promoter microsatellite, in this study we investigate the instability within the region in a range of neoplasms including malignant lymphoma, breast and colon carcinoma and lung adenocarcinoma.
Study Design: A representative sample of CD30+ and CD30- lymphomas and cell lines as well as non-haemopoietic malignancies and normal tissues were typed for CD30 microsatellite length and compared.
Place and Duration of Study: Department of Anatomical Pathology, Pathwest Laboratory Medicine WA, Perth, Australia and School of Chemistry & Biochemistry, University of Western Australia, 2000-2012.
Methodology: DNA was prepared from archived biopsy specimens and used to PCR ampify the CD30 microsatellite region prior to size determination using an Genescan instrument (Applied Biosystems).
Results: This study has identified instability within the CD30 promoter microsatellite region in DNA from the tumour tissue of cases of malignant lymphoma, colon carcinoma and lung adenocarcinoma but not in DNA from benign lymphoid cells or normal tissues.
Conclusion: These findings indicate that variability in the length of the CD30 microsatellite may be a general characteristic of the neoplastic phenotype and may reflect defects in the mismatch repair system in these malignancies rather than a specific feature of CD30-positive neoplasms. Our results suggest that the CD30-MS may be a useful marker to distinguish between normal lymphoid tissue and lymphoid malignancy.
Keywords: Non-Hodgkin Lymphoma, microsatellite instability, TNF receptor family