Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Different pattern of 11q13-14 allelic losses in pancreatic and midgut endocrine tumours

T D’Adda DSc, S Pizzi PhD, C Azzoni PhD, C Bordi MD

Dept Pathology and Laboratory Medicine, Anatomic Pathology, University of Parma, Parma, Italy,

AIMS: The MEN-1 gene, mapping at 11q13, and additional tumour suppressor gene(s) distal to the MEN-1 region have been postulated to be involved in the development of MEN-1 endocrine tumours and their sporadic counterparts. To assess the involvement of these genes in pancreatic endocrine tumours (PETs), that may occur in MEN-1 syndrome, and in ileal and appendicular carcinoids, never associated with the syndrome, a comparative analysis of loss of heterozygosity (LOH) at 11q13-14 region was performed. METHODS: 19 PETs (17 sporadic and 2 MEN-1 associated), 16 ileal carcinoids and 7 appendicular carcinoids were investigated. Seven microsatellite markers (PYGM, D11S4946, D11S913 at 11q13; D11S916 at 11q13-q14 borderline; and D11S901, D11S1365 at 11q14; D11S387 at 11q25) were PCR-amplified using DNA extracted from microdissected, formalin-fixed, paraffin-embedded samples. Fluorescent-tagged amplimers were analyzed with the Genomyx LR/SC DNA sequencer (BeckmanCoulter). RESULTS: In PETs, LOH was observed in 53% of the informative loci. Eight of 17 sporadic, and the 2 MEN-1 tumours showed LOH for all 11q13 markers, consistently extended up to the most distal marker investigated. In contrast, only 10% of the informative loci in midgut carcinoids showed LOH, that were always interstitial and discontinuous. CONCLUSIONS: In PETs, the consistent extension of LOH from the MEN-1 region to 11q14 suggests gene inactivation via chromosomal breakage rather than providing evidence for additional tumour suppressor gene(s). A similar pattern of LOH is not present in midgut carcinoids which, although originating from the same diffuse neuroendocrine system, are not associated with the MEN-1 syndrome.

KEY WORDS: neuroendocrine tumours, polymerase chain reaction.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.