title: Array-based comparative genomic hybridization analysis of high-grade neuroendocrine tumors of the lung.
abstract: We examined a large number of primary high-grade neuroendocrine tumors of the lung (10 small cell lung carcinomas and 31 large cell neuroendocrine carcinomas) by using array-based comparative genomic hybridization using microarrays spotted with 800 bacterial artificial chromosome clones containing tumor-related genes from throughout the human genome. We identified the genome-wide copy number alteration profiles of these tumors, including recurrent amplifications located at 2q21.2, 3q21-27, 3q26, 3q27-29, 5p14.2, 5p13, 7q21.1, 8q21, and 8q24 and homozygous deletions at 1p36, 4p16, 4p16.3, 9p21.3, 9p21, 19p13.3, and 20q13. Our results revealed that small cell lung carcinomas and large cell neuroendocrine carcinomas have multiple characteristic chromosomal alterations in common, but that distinctive alterations also exist between the two subtypes. Moreover, we found that the two subtypes undergo different processes of accumulating these genetic alterations during tumor development. By comparing the genetic profiles with the clinicopathological features, we discovered many chromosomal loci whose alterations were significantly associated with clinical stage and patient prognosis. These results will be valuable for evaluating clinical status, including patient prognosis, and for identifying novel molecular targets for effective therapies.
authors.affiliation: Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Peng
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Hiroto
authors.initials: H
authors.lastname: Katoh
authors.forename: Akiko
authors.initials: A
authors.lastname: Kokubu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tsuchiya
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.forename: Tokuki
authors.initials: T
authors.lastname: Sakiyama
authors.forename: Misao
authors.initials: M
authors.lastname: Ohki
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D018358:Neuroendocrine Tumors / Q000235:genetics*; D009693:Nucleic Acid Hybridization