Biomedical subjects
W Bodmer
Publications and source records attributed to W Bodmer.
Mechanisms of loss of HLA class I expression on colorectal tumor cells.
For several years this laboratory has studied the expression of HLA class I on established colorectal tumor cell lines and on fresh tumors. We review here the mechanisms by which colorectal tumor cells may lose surface expression of HLA class I molecules. Several independent mechanisms have been identified, including loss or mutations in beta 2-microglobulin genes, loss of HLA heavy chain genes, selective lack of expression of HLA alleles, and regulatory defects in HLA expression including loss of expression of the peptide transporters associated with antigen processing (TAP). The data suggest that colorectal tumor cells may evade tumor specific, HLA restricted immune attack by loss of HLA class I expression through a number of mechanisms.
Where will genome analysis lead us forty years on?
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Detection of c-Ki-ras mutations in faecal samples from sporadic colorectal cancer patients.
Colonic exfoliated epithelial cells in faecal material provide a source of human DNA which has been analysed for the presence of the tumour marker ras, in order to detect early tumour cells. The stool samples were subjected to a preliminary sample preparation step followed by centrifugation. DNA was extracted from both the centrifugation pellet and supernatant fractions, as well as from endoscopy washings, using a conventional phenol chloroform extraction method and was then purified on glass milk or spin columns. The purified DNA was amplified using mitochondrial primers and analysed for ras mutations using a non-radioactive, allele specific mismatch method. Corresponding tumour DNA was analysed for mutations using the same method. The results show that approximately 50% of the faecal samples analysed exhibited the presence of ras mutations which were also observed in the corresponding tumours. A double mutation was detected in one supernatant. Our findings represent an important stage in the development of a diagnostic test for the early detection of colorectal cancer.
Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR).
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Genetic steps in colorectal cancer.
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APC mutation associated with late onset of familial adenomatous polyposis.
Familial adenomatous polyposis is an autosomal dominantly inherited disorder. Mutation studies in the corresponding gene (APC) may provide information for predictive tests for persons at risk in affected families. We report here a new mutation in exon 6 (codon 233) of the APC gene and clinical data in a large family with late onset of the disease in most affected persons.
HLA-A locus alleles identified by sequence specific PCR.
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HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer.
An increased frequency of human leukocyte antigen (HLA)-DR1 was found in 49 non-immunosuppressed patients with non-melanoma skin cancer (NMSC), being highest in patients under the age of 60 with multiple squamous cell carcinomas (SCC). Of 266 patients receiving long-term immunosuppression following renal transplantation 46 (17%) were found to have NMSC. No increase in HLA-DR1 was found in renal transplant recipients (RTR) with non-melanoma skin cancer (RTR+C) when compared with matched renal transplant recipients without skin cancer (matched RTR-C), or when compared with healthy controls. There was an increased frequency of DQw2 in RTR+C, most pronounced in RTR with SCC (61.9% compared with 18.75% in matched RTR-C), giving a relative risk of 13.98. We found statistically significant differences in the frequency of a number of HLA antigens on comparing RTR+C with healthy controls, but none of these differences were found when we compared RTR+C against matched RTR-C.
Principles of scientific management.
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A new look at tumour immunology.
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Cancer prevention in central and eastern Europe.
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T-cell immune responses to cancer--a new look.
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The isolation and description of LIF-10: a human tumor cell line derived from a colorectal adenocarcinoma.
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Somatic cell genetics and cancer.
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HIV testing on all pregnant women.
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Identification of HLA-DP polymorphism with DP alpha and DP beta probes and monoclonal antibodies: correlation with primed lymphocyte typing.
Thirty-four lymphoblastoid cell lines that had been previously typed for HLA-DP antigens by primed lymphocyte typing (PLT) were tested by Southern blotting and by ELISA. Using two DP beta probes and a DP alpha probe with a series of enzymes, it is possible to identify restriction fragment length polymorphism (RFLP) patterns characteristic of DPw1, -2, -3, -4, and possibly -5. ELISA typing results, based on two polymorphic DP antibodies DP11.1 and ILR1, were compared with PLT-defined and RFLP-defined types. Thus, using a range of probes and enzymes it is possible to identify DP polymorphism. The value of monoclonal antibodies for such studies is demonstrated, and the molecular data can, in some cases, pinpoint the amino acids responsible for the specificity of the monoclonal antibodies.