Written | 1999-10 | Claude Viguié |
Service de Dermatologie, Hôpital Tarnier-Cochin, 89 rue d'Assas, 75006 Paris, France |
Identity |
Other names | Familial atypical mole-malignant melanoma syndrome (FAMMM) |
B-K mole syndrome | |
Atlas_Id | 10013 |
Genes implicated in | CDKN2A CDKN2C TP53BP1 |
Inheritance | autosomal dominant with high penetrance and variable expressivity; the frequency of DNS is difficult to evaluate because a number of cases without malignant evolution are not recorded; DNS defines patients with numerous dysplastic nevi. FAMMM defines families where coexist numerous nevi with malignant melanoma (MM) sporadic forms of dysplastic nevi are not considered as DNS |
Clinics |
Note | the familial dysplastic nevus syndrome is a good example of a genetic disorder which leads to the practice of self prevention and prevention at the family level; the risk is the evolution towards MM |
Phenotype and clinics | predominant in patients with a clear complexion, blue eyes and/or presence of numerous nevi; the dysplastic nevus or "nevus of Clark" or "atypical melanocytic nevus" is a large mole with a variable size (5 to 15 mm), an irregular border and a color varying from dark brown to depigmentation; lesions are located mainly on the upper trunk, back, limbs, abdomen and arms; the number of moles is variable, from 10 to up to 100 |
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multiple dysplastic naevi on the skin of the bac, with (left) a surgically resected malignant melanoma on the scalp - Courtesy Daniel Wallach | |
Neoplastic risk | the main risk is to develop a MM but there is also a possible increased incidence of pancreatic cancer, breast cancer, and myeloma; MM usually arises from a dysplastic nevus (DN) but it can also appear de novo or from a benign nevus; it occurs most often in the skin but it may also involve other sites, mainly the eye or the central nervous system; the risk of MM depends on three factors: |
Treatment | clinical vigilance and tumour exeresis |
Evolution | the number of DN can increase during life with an increase in MM risk |
Prognosis | according to the tumour expansion at the time of exeresis |
Cytogenetics |
Inborn conditions | a chromosome instability disorder was observed in cell cultures from the normal skin and dysplastic nevi over three-generations in DNS families, leading to translocations, duplications and deletions; in another study on MM, translocations involving bands 11q24, 1q25 and Xq13 were observed in patients with DNS, in dysplastic nevi and in the normal skin as well; a loss of chromosome 9 was found in 2 out of 4 DN, suggesting that deletion / inactivation of a gene on 9p may be a primary event in melanocyte transformation; loss of heterozygocity (LOH) for markers flanking the CDKN2A on 9p was described in primary MM and in a metastasis; other putative tumor suppressor genes which could be involved in the process are located in 1p13, 10p, 10q, 11q and 6q15-q23 DNS is characterized cytogeneticaly by an UV-induced elevated level of sister chromatid exchange (SCE); the post-UV plasmid hypermutability test is a laboratory marker for FAMMM patients, suggesting a defective repair mechanism of UV-induced DNA damage; deficient DNA repair in lymphocyte studies also characterizes some patients with sporadic dysplastic nevi or non familial MM |
Genes involved and Proteins |
Gene Name | still unknown |
Location | 1p36 |
Note | locus in 1p36 (called CMM1 for cutaneous malignant melanoma): this locus segregates with MM and DNS, but no gene is yet cloned |
Gene Name | CDKN2C/p18 (cyclin dependent kinase inhibitor 2C) |
Location | 1p32.3 |
Note | locus in 1p32; this locus has been found mutated in the germline from patients with MM and other tumors |
Gene Name | CDKN2A/p16 (cyclin dependent kinase 2a / p16) |
Location | 9p21.3 |
Note | CDKN2A/p16/MTS1/CDK4 inhibitor (cyclin-dependent kinase inhibitor 2A) ocus in 9p21; this locus has been designated as CMM2; germline mutations were found in this locus in 30 to 40% of patients with FAMMM, and in some patients with two cutaneous and/or mucous MM; P16 is a candidate gene for MM susceptibility; there is a p16 mutation in 10 to 14% of patients suffering from sporadic multifocal MM; P16 is also involved in several other types of cancers; other tumor suppressor genes located at 9p are hypothetically involved in MM progression |
Gene Name | CDK4 (cyclin-dependent kinase 4) |
Location | 12q14.1 |
Note | locus in 12q14; 2 germline mutations found in 3 FAMMM families |
Gene Name | still unknown |
Location | 6q |
Note | locus in 6q: a 6q allelic loss was identified in 21 of 53 informative loci; the chromosomal region bearing the highest frequency of 6q allelic loss was defined by the markers MYB and ESR located at 6q22-q23 and 6q24-q27, respectively; this may indicate genetic heterogeneity |
Gene Name | MC1R (melanocortin 1 receptor) |
Location | 16q24.3 |
Note | locus in 16q24.3; defined as possible susceptibility gene |
Gene Name | TP53 (Tumour protein p53 (Li-Fraumeni syndrome)) |
Location | 17p13.1 |
Note | mutations were found in benign and dysplastic nevi from patients with previous personal or familial history of MM; however, these mutations are considered to be late events and cannot be used as a marker to identify patients at high risk of MM |
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Citation |
This paper should be referenced as such : |
Viguié, C |
Dysplastic nevus syndrome (DNS) |
Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):212-214. |
Free journal version : [ pdf ] [ DOI ] |
On line version : http://AtlasGeneticsOncology.org/Tumors/DysplNevusID10013.html |
Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
Genes | CDK4 | CDKN2A |
External links |
OMIM | 155600 |
OMIM | 155601 |
Orphanet | Familial atypical multiple mole melanoma syndrome |
MeSH | D004416 |
MedGen | D004416 |
UMLS | - |
HGMD | 335362 |
REVIEW articles | automatic search in PubMed |
Last year articles | automatic search in PubMed |
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