PMID- 11238532
OWN - NLM
STAT- MEDLINE
DCOM- 20010405
LR  - 20220309
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 86
IP  - 3
DP  - 2001 Mar
TI  - Multiple allelic deletions and intratumoral genetic heterogeneity in men1 
      pancreatic tumors.
PG  - 1355-61
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple 
      tumors of the endocrine pancreas, the parathyroid, the pituitary, and other 
      tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1 
      tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of 
      23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1 
      patients. Multiple allelic deletions were found. Fractional allelic loss varied 
      from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11, 
      whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over 
      30%. Different lesions from individual patients had discrepant patterns of LOH. 
      Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in 
      most tumor cells, whereas other chromosomal loci were deleted in portions of the 
      analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients 
      with malignant features. Fractional allelic loss did not correlate to malignancy 
      or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to 
      maintain DNA integrity and demonstrate signs of chromosomal instability.
FAU - Hessman, O
AU  - Hessman O
AD  - Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, 
      SE-751 85 Uppsala, Sweden. ola.hessman@kirurgi.uu.se
FAU - Skogseid, B
AU  - Skogseid B
FAU - Westin, G
AU  - Westin G
FAU - Akerstrom, G
AU  - Akerstrom G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Alleles
MH  - Carcinoid Tumor/genetics
MH  - Chromosomes, Human, Pair 11
MH  - Chromosomes, Human, Pair 6
MH  - Duodenal Neoplasms/genetics
MH  - *Gene Deletion
MH  - Genetic Markers
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Thymus Neoplasms/genetics
EDAT- 2001/03/10 10:00
MHDA- 2001/04/06 10:01
CRDT- 2001/03/10 10:00
PHST- 2001/03/10 10:00 [pubmed]
PHST- 2001/04/06 10:01 [medline]
PHST- 2001/03/10 10:00 [entrez]
AID - 10.1210/jcem.86.3.7332 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2001 Mar;86(3):1355-61. doi: 10.1210/jcem.86.3.7332.