Projects / Programmes
Genetics of hereditary melanoma
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B520 |
Biomedical sciences |
General pathology, pathological anatomy |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
melanoma, gena, inheritance
Researchers (7)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0302 |
Institute of Oncology Ljubljana |
Ljubljana |
5055733000 |
0 |
Abstract
In about 5-10% of all patients with cutaneous melanoma (CM), a familial predisposition to develop the melanoma was identified. Among the genes responsible for the development of familial CM, the key one seems to be CDKN2 (cyclin dependent kinase 2A), a highly penetrant tumor suppressor gene. Its penetrance (58% in Europe, 76% in USA and 91% in Australia) depends upon the latitude where the person with mutated gene lives. However, CDKN2A gene mutation can be identified in only about 40% of CM patients who have met the criteria of familial cancer In addition to CDKN2A, two additional highly penetrant genes (CDK4 and ARF) are responsible for familial CM, though in less than 2% of melanoma families.The development of the rest of familial CM cases may be explained by different combinations of low-penetrant genes; the gene most often referred to is gene for MC1R (melanocortin-1 receptor) that codes for the receptor for α-melanocyte stimulating hormone (α -MSH).
In Slovenian melanoma families, we have so far investigated only CDKN2A gene which has been accounted for 45% of all cases of familial CM. In the rest of the cases of familial CM, the causes accountable for the development of the disease may be:
- mutation or specific polymorphism of CDKN2A promotor region
- mutation of CDK4 or ARF genes
- mutation or polymorphism of MC1R
- mutation of other, so far unknown genes
The objective of this project proposal is to investigate the first three genes (CDKN2A promotor region, CDK4 or ARF and MC1R) mentioned above that have not been studied yet in Slovenian population. The results of this study would help us to investigate in details the genes that have been so far known to cause familial CM in our own Slovenian population and thus will enable a rational planning of the genetic counselling and testing in population of Slovenian CM families.
For the proposed project, we will use the DNA bank of Slovenian CM families that have already been tested for CDKN2A mutation and the DNA from new Slovenian CM families who will visit the Melanoma Genetic Clinics at the Institute of Oncology Ljubljana in the following years.
Significance for science
With the research we assesed which genes or their combinations are responsible for hereditary melanma in Slovene population. Additionally, as a part of international GenoMel consortsium we take a part in the discovery of three loci assosiated with development of hereditary melanoma. On the background of all these data it might be possible in the future to construct genomic profile/s of sporadic melanoma which would enable development of new targeted therapies.
Significance for the country
With the transfer of project results into clinics we can enhance in the future the early melanoma detection and treatment potential. Indirectly, this could offer to society a higher number of cured patients with a smaller investment.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
