title: Molecular analysis of isolated tumor glands from endometrial endometrioid adenocarcinomas.
abstract: We studied the extensive molecular alterations of endometrial endometrioid adenocarcinoma (EEA) using a crypt isolation method. We analyzed copy number variation (CNV) using a single nucleotide polymorphism (SNP) array, genetic mutations (KRAS, BRAF, p53, PIK3CA), DNA methylation and microsatellite instability (MSI) status. In addition, loss of PTEN protein expression was examined. Increased chromosome copy numbers of 1q21.2-44 (22%) and 10q11.21-23.31 (28%) were seen relatively frequently in EEA, and copy-neutral loss of heterozygosity (LOH) was also observed in 10q22.1-26.3 (22%). The CNV patterns of EEA were classified into four groups through hierarchical cluster analysis. Cluster 1 had many CNVs of 10q, and cluster 2 was characterized by MSI status. In cluster 3, increased CNVs of 1q were often seen. In cluster 4, p53 mutations were detected. KRAS and PIK3CA mutations and reduced PTEN protein expression were common to all groups. On the other hand, CpG island methylator phenotype (CIMP) was rare in all groups. The data indicated an association with chromosomal gain of 1q and 10q or 10q copy-neutral LOH in some cases. We suggest that EEA consists of four groups that are characterized with molecular alterations.
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan; Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Suga
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Uesugi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fukagawa
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: CIMP; CNV; MSI; PTEN; SNP array; endometrial endometrioid adenocarcinoma