Abstract:
:Genome-wide analyses of human lung adenocarcinoma have identified regions of consistent copy-number gain or loss, but in many cases the oncogenes and tumor suppressors presumed to reside in these loci remain to be determined. Here we identify the downstream of tyrosine kinase (Dok) family members Dok1, Dok2 and Dok3 as lung tumor suppressors. Single, double or triple compound loss of these genes in mice results in lung cancer, with penetrance and latency dependent on the number of lost Dok alleles. Cancer development is preceded by an aberrant expansion and signaling profile of alveolar type II cells and bronchioalveolar stem cells. In human lung adenocarcinoma, we identify DOK2 as a target of copy-number loss and mRNA downregulation and find that DOK2 suppresses lung cancer cell proliferation in vitro and in vivo. Given the genomic localization of DOK2, we propose it as an 8p21.3 haploinsufficient human lung tumor suppressor.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Berger AH,Niki M,Morotti A,Taylor BS,Socci ND,Viale A,Brennan C,Szoke J,Motoi N,Rothman PB,Teruya-Feldstein J,Gerald WL,Ladanyi M,Pandolfi PPdoi
10.1038/ng.527subject
Has Abstractpub_date
2010-03-01 00:00:00pages
216-23issue
3eissn
1061-4036issn
1546-1718pii
ng.527journal_volume
42pub_type
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