Title |
High Frequency Strand Slippage Mutations in CTCF in MSI‐Positive Endometrial Cancers
|
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Published in |
Human Mutation, November 2013
|
DOI | 10.1002/humu.22463 |
Pubmed ID | |
Authors |
Israel Zighelboim, David G. Mutch, Amy Knapp, Li Ding, Mingchao Xie, David E. Cohn, Paul J. Goodfellow |
Abstract |
Tumors with defective mismatch repair acquire large numbers of strand slippage mutations including frameshifts in coding sequence repeats. We identified a mutational hotspot, p.T204fs, in the insulator-binding protein (CTCF) in MSI-positive endometrial cancers. Although CTCF was described as a significantly mutated gene by the endometrial cancer TCGA, the A₇ track variants leading to T204 frameshifts were not reported. Reanalysis of TCGA data using Pindel revealed frequent T204fs mutations, confirming CTCF is an MSI target gene and revealed the same frameshifts in tumors with intact mismatch repair. We show that T204fs transcripts are subject to nonsense-mediated decay and as such, T204fs mutations are unlikely to act as dominant negatives. The spectrum and pattern of mutations observed is consistent with CTCF acting as a haploinsufficient tumor suppressor. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 5% |
Unknown | 20 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 19% |
Other | 3 | 14% |
Researcher | 3 | 14% |
Student > Master | 3 | 14% |
Student > Bachelor | 2 | 10% |
Other | 0 | 0% |
Unknown | 6 | 29% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 7 | 33% |
Agricultural and Biological Sciences | 3 | 14% |
Computer Science | 1 | 5% |
Physics and Astronomy | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Other | 0 | 0% |
Unknown | 8 | 38% |