University of Newcastle Upon Tyne Cancer Research Unit

The role of defects of the DNA mismatch repair system in the pathogenesis of plasma cell dyscrasias

Interest in the mismatch repair (MMR) system has been stimulated by the finding of germline mutations in hMSH2 and hMLH1 can be detected in over 50% of cases of hereditary non-polyposis colon cancer and that somatic mutations in these genes can be found in a subset of cases of sporadic tumours arising in ovary, breasts, cervix, endometrium, lung and pancreas. An increased predisposition to form tumours, especially lymphomas, has also been noted in mice with germline deletions of MLH1, MSH2 or PMS2.

As well as being involved in the aetiology of a wide range of malignancies, defects in MMR have been implicated in the development of drug resistance to a number of cytotoxic drugs eg. doxorubicin.

We are currently studying the incidence of these defects in a variety of haematological malignancies, including MGUS, multiple myeloma and plasma cell leukaemia.

Staff involved:

Contact addresses

AH/JI/MV
Cancer Research Unit
Medical School
University of Newcastle Upon Tyne
Email: ms.velangi@btinternet.com

PT/GJ
Dept Haematology
Royal Victoria Infirmary
Newcastle Upon Tyne
Email: graham.jackson@ncl.ac.uk

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