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

Daniel Hagerstrand1, Alexander Tong, Steven E Schumacher

  • 11Departments of Medical Oncology and 2Cancer Biology; 3Center for Cancer Genome Discovery, Dana-Farber Cancer Institute;4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; 5Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and 6Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina.

Cancer Discovery
|June 15, 2013
PubMed
Abstract

Insights

Researchers identified TLOC1 and SKIL as key cancer driver genes within the 3q26 amplified region. These genes promote tumor growth and invasion, highlighting the importance of co-amplified genes in cancer development.

Area of Science:

  • Genetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • The 3q26 chromosomal region is frequently amplified in various cancers, containing approximately 20 genes.
  • Identifying specific driver genes within amplified regions is crucial for understanding cancer development and identifying therapeutic targets.

Purpose of the Study:

  • To identify cancer driver genes within the amplified 3q26 region.
  • To elucidate the functional roles of TLOC1 and SKIL in cancer cell proliferation, growth, and invasion.

Main Methods:

  • Utilized loss- and gain-of-function genetic screens to interrogate gene function.
  • Performed proteomic studies to identify protein interactions.
  • Assessed anchorage-independent growth, cell invasion, and subcutaneous tumor formation.

Main Results:

  • TLOC1 (SEC62) was essential for the proliferation of cancer cells with 3q26 amplification and induced anchorage-independent growth.
  • SKIL (SNON) promoted cell invasion, and co-expression of TLOC1 and SKIL led to subcutaneous tumor growth.
  • TLOC1 interacts with DDX3X, impacting protein translation, while SKIL upregulates SLUG (SNAI2) to enhance invasion.

Conclusions:

  • TLOC1 and SKIL are identified as driver genes within the 3q26 amplified region.
  • Co-amplified genes in regions of somatic copy number gain can possess complementary functions, driving cancer progression.

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