Biomedical subjects

D R Lohmann

Publications and source records attributed to D R Lohmann.

22 records · Page 2Linked to original sources

PubMed1994

Distinct RB1 gene mutations with low penetrance in hereditary retinoblastoma.

The interfamilial diversity in penetrance and expressivity of hereditary retinoblastoma was investigated in 29 families. By using a simple parameter for estimating the severity of the disease (diseased-eye-ratio), we were able to identify four families with a discrete low-penetrance phenotype. The underlying genetic defect was identified in three families. One family has a 3-bp deletion in exon 16 that results in the deletion of Asn480. In two further unrelated families, the identical missense mutation at codon 661 in exon 20 (CGG to TGG, Arg to Trp) was identified. These mutations are distinct from the majority of retinoblastoma gene alterations, as they do not result in the disruption of the gene product. We propose that reduced penetrance of retinoblastoma is the result of a residual function of these alleles in retinoblastoma precursor cells.

Base Sequence↗

PubMed1994

Spectrum of small length germline mutations in the RB1 gene.

A screening method based on multiplexed automated fragment length analysis of polymerase chain reaction products was used to identify germline mutations in the RB1 gene. By screening 106 unrelated patients with hereditary retinoblastoma, 20 small deletions (1-18 bp) and seven insertions (1-5 bp) were identified. When collating our data with reported mutations, recurrence of small length mutations was observed at nine sites within the RB1 gene. Most of these contained monotonic runs or direct repeats embedded in homocopolymer tracts. While the majority of mutations resulted in premature truncation, two mutations caused an in-frame loss of F755 and G540 to E545, respectively. A genotype-phenotype comparison of patients carrying different small length mutations did not reveal any consistent relation. Particularly, the two patients with in-frame mutations showed a high number of tumours consistent with regular-penetrance retinoblastoma.

Base Sequence↗

PubMed1993

Infrequent mutations of the p53 gene in pulmonary carcinoid tumors.

Archival specimens of 25 pulmonary carcinoids including 15 cases of typical carcinoid, 9 atypical carcinoids, and 1 large-cell neuroendocrine carcinoma were analyzed for mutations in exons 5 to 8 of the p53 gene. Mutations were identified in 4 tumors, including 3 out of 15 (20%) typical carcinoids and the single large-cell neuroendocrine carcinoma, but none of the atypical carcinomas showed a mutation. The mutations were acquired during tumor development since they were not present in the corresponding nontumorous tissue. All mutations in the typical carcinoids, a tumor type without epidemiological link to cigarette smoking, were G to A transitions. The level of p53 protein was investigated by immunohistochemistry with the polyclonal antibody CM-1. None of the pulmonary carcinoids investigated showed a positive reaction, despite the presence of missense mutations in two cases. Negative staining of carcinoids with mutations was also observed with the monoclonal antibodies pAb1801 and DO-1. Our data suggest that point mutations of the p53 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer. Moreover, negative immunostaining for p53 is no indicator for the absence of p53 missense mutations in typical carcinoids.

Adult↗

PubMed1993

Identification of p53 gene mutations in gastrointestinal and pancreatic carcinoids by nonradioisotopic SSCA.

A nonisotopic screening method based on single-strand DNA conformation analysis (SSCA) was established for the identification of p53 gene alterations in achieved tissue samples. The sensitivity of this approach was validated by testing mutations previously identified by direct sequencing. Applying this assay, 40 samples of formalin-fixed, paraffin-embedded tumors, including 33 gastrointestinal carcinoids and seven endocrine pancreatic tumors, were screened. Only one mutation (codon 283, CGC to CCC) was identified in a single clinically benign rectal carcinoid. This mutation occurred during the development of the tumor and was accompanied by loss of the wild-type gene. Our data indicate, that, in contrast to gastrointestinal carcinomas, alterations of the p53 gene are infrequent events in the development of gastrointestinal and pancreatic carcinoids. In addition, there was no evidence for the involvement of p53 in the malignant metastatic progression of carcinoids.

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