Identification of Las2, a major modifier gene affecting the Pas1 mouse lung tumor susceptibility locus

Peng Yuan Liu, Haris Vikis, Michael James, Yan Lu, Dao Long Wang, Hong Bo Liu, Wei Dong Wen, Yian Wang, Ming You

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Lung cancer is the leading cause of cancer death worldwide. Here, we describe a genome-wide association study of chemically induced lung tumorigenesis on 593 mice from 21 inbred strains using 115,904 genotyped and 1,952,918 imputed single nucleotide polymorphisms (SNPs). Using a genetic background-controlled genome search, we identified a novel lung tumor susceptibility gene Las2 (Lung adenoma susceptibility 2) on distal chromosome 18. Las2 showed strong association with resistance to tumor induction (rs30245983; P = 1.87 × 10-9) as well as epistatic interactions (P = 1.71 × 10-3) with the pulmonary adenoma susceptibility 1 locus, a major locus affecting mouse lung tumor development (rs13459098, P = 5.64 × 10-27). Sequencing analysis revealed four nonsynonymous SNPs and two insertions/deletions in the susceptible allele of Las2, resulting in the loss of tumor suppressor activities in both cell colony formation and nude mouse tumorigenicity assays. Deletion of LAS2 was observed in ∼ 40% of human lung adenocarcinomas, implying that loss of function of LAS2 may be a key stepfor lung tumorigenesis.

Original languageEnglish (US)
Pages (from-to)6290-6298
Number of pages9
JournalCancer research
Issue number15
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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