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Characterizing the cancer genome in lung adenocarcinoma | | Barbara A Weir
; Michele S Woo
; Gad Getz
; Sven Perner
; Li Ding
; Rameen Beroukhim
; William M Lin
; Michael A Province
; Aldi Kraja
; Laura A Johnson
; Kinjal Shah
; Mitsuo Sato
; Roman K Thomas
; Justine A Barletta
; Ingrid B Borecki
; Stephen Broderick
; Andrew C Chang
; Derek Y Chiang
; Lucian R Chirieac
; Jeonghee Cho
; Yoshitaka Fujii
; Adi F Gazdar
; Thomas Giordano
; Heidi Greulich
; Megan Hanna
; Bruce E Johnson
; Mark G Kris
; Alex Lash
; Ling Lin
; Neal Lindeman
; Elaine R Mardis
; John D McPherson
; John D Minna
; Margaret B Morgan
; Mark Nadel
; Mark B Orringer
; John R Osborne
; Brad Ozenberger
; Alex H Ramos
; James Robinson
; Jack A Roth
; Valerie Rusch
; Hidefumi Sasaki
; Frances Shepherd
; Carrie Sougnez
; Margaret R Spitz
; Ming-Sound Tsao
; David Twomey
; Roel G W Verhaak
; George M Weinstock
; David A Wheeler
; Wendy Winckler
; Akihiko Yoshizawa
; Soyoung Yu
; Maureen F Zakowski
; Qunyuan Zhang
; David G Beer
; Ignacio I Wistuba
; Mark A Watson
; Levi A Garraway
; Marc Ladanyi
; William D Travis
; William Pao
; Mark A Rubin
; Stacey B Gabriel
; Richard A Gibbs
; Harold E Varmus
; Richard K Wilson
; Eric S Lander
; Matthew Meyerson
; | | Date: |
4 Nov 2007 | | Journal: | Nature, (), | | Abstract: | Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in approximately 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered. | | Source: | PubMed, pmid17982442 doi: 10.1038/nature06358 | | Services: | Forum | Review | Favorites | |
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