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Cancer discovery DOI:10.1158/2159-8290.CD-12-0592

Systematic interrogation of 3q26 identifies TLOC1 and SKIL as cancer drivers.

Publication TypeJournal Article
Year of Publication2013
AuthorsHagerstrand, D, Tong, A, Schumacher, SE, Ilic, N, Shen, RR, Cheung, HW, Vazquez, F, Shrestha, Y, Kim, SY, Rosenbluh, J, Schinzel, AC, Barbie, DA, Mermel, CH, Weir, BA, Garraway, LA, Tamayo, P, Mesirov, JP, Beroukhim, R, Hahn, WC
JournalCancer discovery
Date Published2013/06/13

3q26 is frequently amplified in several cancer types with a common amplified region containing 20 genes. To identify cancer driver genes in this region, we interrogated the function of each of these genes by loss- and gain-of-function genetic screens. Specifically, we found that TLOC1 (SEC62) was selectively required for the proliferation of cell lines with 3q26 amplification. Increased TLOC1 expression induced anchorage independent growth and a second 3q26 gene, SKIL (SNON), facilitated cell invasion in immortalized human mammary epithelial cells. Expression of both TLOC1 and SKIL induced subcutaneous tumor growth. Proteomic studies demonstrated that TLOC1 binds to DDX3X, which is essential for TLOC1-induced transformation and affected protein translation. SKIL induced invasion through up-regulation of SLUG (SNAI2) expression. Together, these studies identify TLOC1 and SKIL as driver genes at 3q26 and more broadly suggest that cooperating genes may be co-amplified in other regions with somatic copy number gain.