| Title |
The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies
|
|---|---|
| Published in |
Orphanet Journal of Rare Diseases, March 2015
|
| DOI | 10.1186/s13023-015-0231-z |
| Pubmed ID | |
| Authors |
Carla Colombo, Emanuela Minna, Maria Grazia Rizzetti, Paola Romeo, Daniele Lecis, Luca Persani, Piera Mondellini, Marco A Pierotti, Angela Greco, Laura Fugazzola, Maria Grazia Borrello |
| Abstract |
Hereditary medullary thyroid carcinoma (MTC) is caused by germ-line gain of function mutations in the RET proto-oncogene, and a phenotypic variability among carriers of the same mutation has been reported. We recently observed this phenomenon in a large familial MTC (FMTC) family carrying the RET-S891A mutation. Among genetic modifiers affecting RET-driven MTC, a role has been hypothesized for RET-G691S non-synonymous polymorphism, though the issue remains controversial. Aim of this study was to define the in vitro contribution of RET-G691S to the oncogenic potential of the RET-S891A, previously shown to harbour low transforming activity. The RET-S891A and RET-G691S/S891A mutants were generated by site-directed mutagenesis, transiently transfected in HEK293T cells and stably expressed in NIH3T3 cells. Their oncogenic potential was defined by assessing the migration ability by wound healing assay and the anchorage-independent growth by soft agar assay in NIH3T3 cells stably expressing either the single or the double mutants. Two RET-S891A families were characterised for the presence of RET-G691S. The functional studies demonstrated that RET-G691S/S891A double mutant displays a higher oncogenic potential than RET-S891A single mutant, assessed by focus formation and migration ability. Moreover, among the 25 RET-S891A carriers, a trend towards an earlier age of diagnosis was found in the MTC patients harboring RET-S891A in association with RET-G691S. We demonstrate that the RET-G691S non-synonymous polymorphism enhances in vitro the oncogenic activity of RET-S891A. Moreover, an effect on the phenotype was observed in the RET-G691S/S891A patients, thus suggesting that the analysis of this polymorphism could contribute to the decision on the more appropriate clinical and follow-up management. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 15% |
| Researcher | 4 | 10% |
| Student > Master | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Student > Bachelor | 2 | 5% |
| Other | 9 | 23% |
| Unknown | 11 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 38% |
| Biochemistry, Genetics and Molecular Biology | 8 | 21% |
| Agricultural and Biological Sciences | 2 | 5% |
| Business, Management and Accounting | 1 | 3% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 01 March 2015.
All research outputs
#20,263,155
of 22,793,427 outputs
Outputs from Orphanet Journal of Rare Diseases
#2,459
of 2,615 outputs
Outputs of similar age
#216,374
of 256,543 outputs
Outputs of similar age from Orphanet Journal of Rare Diseases
#25
of 27 outputs
Altmetric has tracked 22,793,427 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,615 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 256,543 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.