| Title |
The genomic and transcriptomic landscape of anaplastic thyroid cancer: implications for therapy
|
|---|---|
| Published in |
BMC Cancer, December 2015
|
| DOI | 10.1186/s12885-015-1955-9 |
| Pubmed ID | |
| Authors |
Katayoon Kasaian, Sam M. Wiseman, Blair A. Walker, Jacqueline E. Schein, Yongjun Zhao, Martin Hirst, Richard A. Moore, Andrew J. Mungall, Marco A. Marra, Steven JM Jones |
| Abstract |
Anaplastic thyroid carcinoma is the most undifferentiated form of thyroid cancer and one of the deadliest of all adult solid malignancies. Here we report the first genomic and transcriptomic profile of anaplastic thyroid cancer including those of several unique cell lines and outline novel potential drivers of malignancy and targets of therapy. We describe whole genomic and transcriptomic profiles of 1 primary anaplastic thyroid tumor and 3 authenticated cell lines. Those profiles augmented by the transcriptomes of 4 additional and unique cell lines were compared to 58 pairs of papillary thyroid carcinoma and matched normal tissue transcriptomes from The Cancer Genome Atlas study. The most prevalent mutations were those of TP53 and BRAF; repeated alterations of the epigenetic machinery such as frame-shift deletions of HDAC10 and EP300, loss of SMARCA2 and fusions of MECP2, BCL11A and SS18 were observed. Sequence data displayed aneuploidy and large regions of copy loss and gain in all genomes. Common regions of gain were however evident encompassing chromosomes 5p and 20q. We found novel anaplastic gene fusions including MKRN1-BRAF, FGFR2-OGDH and SS18-SLC5A11, all expressed in-frame fusions involving a known proto-oncogene. Comparison of the anaplastic thyroid cancer expression datasets with the papillary thyroid cancer and normal thyroid tissue transcriptomes suggested several known drug targets such as FGFRs, VEGFRs, KIT and RET to have lower expression levels in anaplastic specimens compared with both papillary thyroid cancers and normal tissues, confirming the observed lack of response to therapies targeting these pathways. Further integrative data analysis identified the mTOR signaling pathway as a potential therapeutic target in this disease. Anaplastic thyroid carcinoma possessed heterogeneous and unique profiles revealing the significance of detailed molecular profiling of individual tumors and the treatment of each as a unique entity; the cell line sequence data promises to facilitate the more accurate and intentional drug screening studies for anaplastic thyroid cancer. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| France | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 63 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 20 | 32% |
| Student > Ph. D. Student | 12 | 19% |
| Other | 7 | 11% |
| Student > Bachelor | 5 | 8% |
| Professor > Associate Professor | 5 | 8% |
| Other | 8 | 13% |
| Unknown | 6 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 24 | 38% |
| Medicine and Dentistry | 14 | 22% |
| Agricultural and Biological Sciences | 9 | 14% |
| Nursing and Health Professions | 3 | 5% |
| Immunology and Microbiology | 2 | 3% |
| Other | 3 | 5% |
| Unknown | 8 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 February 2019.
All research outputs
#6,427,356
of 22,835,198 outputs
Outputs from BMC Cancer
#1,635
of 8,309 outputs
Outputs of similar age
#101,934
of 388,246 outputs
Outputs of similar age from BMC Cancer
#31
of 184 outputs
Altmetric has tracked 22,835,198 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 8,309 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 79% of its peers.
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We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.