Genetic rearrangements in neuro-endocrine breast tumors.

Genetic rearrangements in neuro-endocrine breast tumors.

223 Abstracts 17 GENETIC A. Bootsma*, REARRANGEMENTS A.de Klein IN NEURO-ENDOCRINE # and S.W.J.Lamberts * Dept. Internal Medicine III Genetic...

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223

Abstracts 17

GENETIC A.

Bootsma*,

REARRANGEMENTS A.de

Klein

IN NEURO-ENDOCRINE

# and

S.W.J.Lamberts

* Dept. Internal Medicine III Genetics, Erasmus University, Rotterdam. The Netherlands.

and # P.O.

BREAST

TUMORS.

*.

dept. Cellbiology Box 1738, 3000

and DR

Oncogenes and tumor suppressor genes are involved in t h e etiology of human cancer. Since breast cancer is pathologically a heterogeneous disease it is interesting to investigate whether certain genetic changes can be correlated with specific subgroups of these tumors. Thus far amplification of neu, int-2 and the myc oncogenes and loss of p53 and retinoblastoma genes have been reported. Overexpression of the neu gene was found to occur mainly in comedo type ductal carcinomas. Twenty percent of all breast tumors express the somatostatin receptor. I t h a s b e e n s h o w n b y R e u b i e t al. t h a t t h e g r o u p of somatostatin receptor positive breast tumors overlaps with the breast tumors that have neuroendocrine characteristics. In small cell lung carcinoma,also neuroendocrine tumor it was demonstrated t h a t in 6 0 % o f t h e c a s e s t h e r e t i n o b l a s t o m a gene was inactivated. We have investigated whether mutations in the retinoblastoma gene, which are found in 25% of all breast tumors, correlates with this neuroendocrine subgroup. To this e n d 49 p r i m a r y breast cancers were analysed for expression of the somatostatin receptor, neuroendocrine characteristics and deletions of the retinoblastoma gene. The tumorspecimens were also used to investigate genetic alterations and/or amplification of the neu, int-2 and myc oncogenes.

18 DISTRIBUTION OF LOSSES OF CONSTITUTIONAL CANCER I. VORECHOVSKY,

G.R.M.

HETEROZYGOSITY

AT 17DII{ IN BREAST

WHITE, M. SANTIBANEZ-KOREF

CRC, DEPARTMENT OF CANCER CENETICS, MANCHESTER MS0 9BX, UK.

PATERSON INSTITUTE FOR CANCER RESEARCH,

Loss of constitutional heterozygosity (LOCH) on the short arm of chromosome 17 has been recognised as a frequent event in breast cancer development. Eighty eight patients with primary breast cancer were screened for LOCH with two highly polymorphic markers YNZ22.1 and 144-D6. Fifty patients were found informative for both loci. Apart from 10 cases with LOCH in both loci, twelve out of 50 cases had LOCH detected by YNZ22.1, but retained heterozygosity at the more distal locus. However, five patients were identified exhibiting LOCH detected by 144-D6 and no loss at the more proximal locus. If there were a single common area of deletion involvin~ the p53 sene, which is centromeric to YNZ22.1, the latter combination would not be expected or would be present only if more than one deletion (event) occurred in this region. Because the number of patients with the former combination is higher than with the latter it appears that the most frequent region for deletion is closer to YNZ22.1 than 144-D6. However, since we could not exclude that these two losses are independent events (p>O.05), it is possible that at 17p13 in human breast cancer there is more than one, or even a variety of different deletions/rearraneements with no consistent single area of minimal deletion invariably present in all breast tumours.