Loss of heterozygosity studies at the retinoblastoma and breast cancer susceptibility (BRCA2) loci in pituitary, parathyroid, pancreatic and carcinoid tumours.
OBJECTIVE
Allelic deletion of the retinoblastoma (Rb) gene on chromosome 13 has been reported in both pituitary and parathyroid tumours. We have investigated the roles of the Rb and the hereditary breast cancer susceptibility gene (BRCA2), which lie within 25 cM of each other on chromosome 13q12-14, in the multi-step aetiology of endocrine tumours.


METHODS
Seventy-seven endocrine tumours (43 anterior pituitary, 22 parathyroid, 7 carcinoid, and 5 pancreatic islet cell tumours) with paired leucocytes have been examined for loss of heterozygosity (LOH) at the Rb and BRCA2 loci by using specific oligonucleotide primers for the PCR amplification of microsatellite polymorphisms at three intragenic Rb markers, Rb1.20, Rbi4 and D13S153, and D13S260 which is linked to the BRCA2 locus.


RESULTS
Seventy-five of the 77 tumour-leucocyte pairs were informative and LOH was detected in 1 of 16 non-functioning pituitary tumours, 1 of 8 prolactinomas, 3 of 19 parathyroid adenomas and 1 of 1 parathyroid carcinoma. All the 3 parathyroid adenomas with LOH were associated with aggressive clinical and histopathological features. Allele loss was not detected in any of the 16 somatotrophinomas, 2 corticotrophinomas, 1 gonadotrophinoma, 7 carcinoid tumours (6 bronchial, 1 metastatic intestinal) or 5 pancreatic islet cell tumours that were informative.


CONCLUSIONS
These results demonstrate that allelic deletions of the 13q12-14 region occur in some pituitary adenomas and 16% of parathyroid adenomas. The extensive loss, which involves both the Rb gene and the BRCA2 locus, suggests that tumour suppressor genes in this region other than Rb or BRCA2 may be involved in the development and progression of some endocrine tumours.
Pearce
S H
SH
MRC Molecular Endocrinology Group, Royal Postgraduate Medical School, London, UK.
Trump
D
D
Wooding
C
C
Sheppard
M N
MN
Clayton
R N
RN
Thakker
R V
RV
D024682:BRCA2 Protein; D002276:Carcinoid Tumor / Q000235:genetics; D002882:Chromosomes, Human, Pair 13; D017931:DNA Primers / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D010282:Parathyroid Neoplasms / Q000235:genetics; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D017931:DNA Primers; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors