Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation Journal Article


Authors: Morris, L. G. T.; Kaufman, A. M.; Gong, Y.; Ramaswami, D.; Walsh, L. A.; Turcan, S.; Eng, S.; Kannan, K.; Zou, Y.; Peng, L.; Banuchi, V. E.; Paty, P.; Zeng, Z.; Vakiani, E.; Solit, D.; Singh, B.; Ganly, I.; Liau, L.; Cloughesy, T. C.; Mischel, P. S.; Mellinghoff, I. K.; Chan, T. A.
Article Title: Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation
Abstract: Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding β-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology: the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor. © 2013 Nature America, Inc. All rights reserved.
Journal Title: Nature Genetics
Volume: 45
Issue: 3
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2013-03-01
Start Page: 253
End Page: 261
Language: English
DOI: 10.1038/ng.2538
PROVIDER: scopus
PUBMED: 23354438
PMCID: PMC3729040
DOI/URL:
Notes: --- - "Export Date: 1 April 2013" - "CODEN: NGENE" - "Source: Scopus"
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MSK Authors
  1. Timothy Chan
    227 Chan
  2. Stella Lee Eng
    6 Eng
  3. Philip B Paty
    373 Paty
  4. Bhuvanesh Singh
    208 Singh
  5. David Solit
    440 Solit
  6. Zhaoshi Zeng
    85 Zeng
  7. Luc Morris
    129 Morris
  8. Ian Ganly
    238 Ganly
  9. Yongxing Gong
    7 Gong
  10. Sevin Turcan
    25 Turcan
  11. Efsevia Vakiani
    165 Vakiani
  12. Logan Alexander Walsh
    19 Walsh
  13. Kasthuri Srinivasan Kannan
    11 Kannan
  14. Yilong Zou
    13 Zou
  15. Luke C Peng
    3 Peng