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Molecular analysis of isolated tumor glands from endometrial endometrioid adenocarcinomas
Author(s) -
Suga Yasuko,
Sugai Tamotsu,
Uesugi Noriyuki,
Kawasaki Tomonori,
Fukagawa Tomoyuki,
Yamamoto Eiichiro,
Ishida Kazuyuki,
Suzuki Hiromu,
Sugiyama Toru
Publication year - 2015
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12274
Subject(s) - pten , kras , microsatellite instability , biology , loss of heterozygosity , cancer research , copy number variation , comparative genomic hybridization , genetics , chromosome , mutation , allele , gene , microsatellite , pi3k/akt/mtor pathway , genome , apoptosis
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.