Allelotype of pancreatic adenocarcinoma using xenograft enrichment.
p53 and MTS1 are known to be mutationally inactivated in pancreatic adenocarcinoma. Other tumor suppressor genes are likely also to play a role. To define chromosomal arms which may harbor additional tumor suppressor genes, we performed an extensive allelotype on pancreatic cancer utilizing a xenograft enrichment technique. Eighty-eight percent (28/32) of primary tumors gave rise to xenografts. Eighteen cases were used in a PCR-based allelotype using 283 polymorphic markers, over 2800 informative assays, and an average coverage of 4.1 informative markers per chromosomal arm per case. Highly frequent allelic loss (> 60%) was seen at chromosomes 1p, 9p, 17p, and 18q. Moderately frequent allelic loss (40-60%) was seen at 3p, 6p, 6q, 8p, 10q, 12q, 13q, 18p, 21q, and 22q. The average fractional allelic loss was 0.36. Allelic and sequence stability was demonstrated among 64 parallel and second-passage xenografts derived from 12 cases of pancreatic adenocarcinoma with the ascertainment of over 3000 single alleles. The findings were confirmed in primary tumors. In only two instances were discrepancies revealed between the allelic loss data obtained from corresponding parallel xenografts, probably due to the xenografting of minor subpopulations, reflecting genetic heterogeneity of the primary tumor.
Hahn
S A
SA
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Seymour
A B
AB
Hoque
A T
AT
Schutte
M
M
da Costa
L T
LT
Redston
M S
MS
Caldas
C
C
Weinstein
C L
CL
Fischer
A
A
Yeo
C J
CJ
D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017354:Point Mutation; D017384:Sequence Deletion; D014183:Transplantation, Heterologous
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm