title: Whole genome comparison of allelic imbalance between noninvasive and invasive small-sized lung adenocarcinomas.
abstract: Seventy-two small-sized (<or=2 cm in diameter) lung adenocarcinomas consisting of 15 noninvasive and 57 invasive tumors were subjected to whole genome allelic imbalance (AI) scanning and mutational analysis of the EGFR, KRAS, and TP53 genes to elucidate genetic pathways of early-stage lung adenocarcinomas. The chromosome 13q13 region showed the most frequent AI (58%) and was affected at similar frequencies between noninvasive and invasive tumors (53% and 60%, respectively), as EGFR and KRAS mutations were. The number of AI regions as well as the frequency of TP53 mutations in invasive tumors was significantly higher than those in noninvasive ones [9.8 +/- 5.6 versus 4.8 +/- 2.8 (P = 0.00002) and 61% versus 13% (P = 0.001), respectively]. In particular, AIs at the chromosome 11p11-p12, 17p12-p13, and 18p11 regions in invasive tumors were significantly more frequent than those in noninvasive ones (P < 0.01). The results indicated that noninvasive tumors were developed by EGFR, KRAS, and 13q alterations and progressed to invasive ones by subsequent alterations of several tumor suppressor genes, including those on 11p11-p12, 17p12-p13, and 18p11 and TP53. AI at 8p21 was significantly more frequent in advanced stages (>IA) and associated with worse prognoses (P = 0.04) and, thus, would be involved in invasion and/or metastasis of adenocarcinoma cells and useful for the prediction of prognosis of patients with small-sized lung adenocarcinoma.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D022981:Allelic Imbalance / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins