Xq25 and Xq26 identify the common minimal deletion region in malignant gastroenteropancreatic endocrine carcinomas.
Loss of heterozygosity (LOH) for markers on X chromosome are associated with malignancy in endocrine tumors of the stomach and pancreas. The aim of this work is to investigate low-grade, well-differentiated endocrine carcinomas (WDEC) vs high-grade, poorly differentiated endocrine carcinomas (PDEC) of the gastroenteropancreatic (GEP) tract for common deletion regions on X chromosome. We performed a comparative allelotyping analysis with 24 highly polymorphic markers for the X chromosome in 12 WDECs and 5 PDECs. Overall, the LOH frequency in all informative loci investigated was 59% in primary and 61% in metastasis, with a significantly higher rate in PDECs than in WDECs (p<0.015 for primary and p<0.00005 for metastasis). In both WDECs and PDECs, the small Xq25 region as defined by DXS8059, DXS8098, and DXS8009 markers showed higher LOH rate as compared to the rest of the chromosome markers (p<0.04). In addition, LOH was very frequently elevated also in DXS294 and in DXS102 loci mapping the chromosomal region Xq26. In no instances differences were found between primary tumors and metastases. Methylation analysis revealed that Xq25 loss preferentially occurred on the inactive X chromosome, a feature in agreement with findings from other human cancers suggesting escape of tumor suppressor genes to X chromosome inactivation at this region. Overall, our data indicate that the two chromosomal regions, Xq25 and Xq26, may participate to the malignant progression of GEP endocrine carcinomas.
Azzoni
Cinzia
C
Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Via Gramsci 14, 43100 Parma, Italy.
Bottarelli
Lorena
L
Pizzi
Silvia
S
D'Adda
Tiziana
T
Rindi
Guido
G
Bordi
Cesare
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004379:Duodenal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009693:Nucleic Acid Hybridization / Q000379:methods; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9