Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes of 24 individuals, following diagnosis, and prior to surgical removal, of a sporadic dysplastic nevus (DN). Lower SCE values and variability were found in 23 sporadic DN individuals compared with controls (2.52+0.12 and 3.76±0.22 SCE/cell, respectively). These DN individuals, contrarily to healthy controls and some types of tumor patients whose cells are hypersensitive to mutagenic agents, did not show increased SCE rates as a consequence of cigarette smoking, alcohol consumption and diagnostic radiation treatments. These observations are in contrast with clinical evidence that similar lesions are both markers or risk and precursors of malignancy in individuals with multiple nevi, affected by the dysplastic nevus syndrome (DNS) or belonging to FMM (familial malignant melanoma) families. Three HLA class I alleles out of 72 tested were found more frequently in sporadic DN individuals compared with controls: B37 (p<0.05), B52 (p<0.01) and B70 (p<0.01). Whether the greater chromosomal stability (as shown by the SCE analysis), and/or the altered frequency of some HLA alleles could influence the chance of developing cutaneous malignancy in DN individuals is yet to be evaluated.
BaleS.J., DracopoliN.C., TukerM.A.Mapping of the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p.N Engl J Med1989; 320: 1367–72.
8.
KangS.W., BarnhillR.L., MihmM.C.. Melanoma risk in individuals with clinically atypical nevi.Arch Dermatol1994; 130: 999–1001.
9.
Van HaeringenA., BergmanW., NelenM.R.. Exclusion of the dysplastic nevus syndrome (DNS) locus from the short arm of chromosome 1 by linkage studies in Dutch families.Genomics1989; 5: 61–4.
10.
Cannon-AlbrightL.A., GoldgarD.E., WrightE.C.. Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome lp36.Am J Hum Genet1990; 46: 912–8.
11.
NancarrowD.J., PalmerJ.M., WaltersM.K.. Exclusion of the familial melanoma locus (MLM) from the PND/D 1S47 and MYCL1 regions of chromosome arm 1p in 7 Australian pedigrees.Genomics1992; 12: 18–25.
12.
DracopoliN.C., FountainJ.W.CDKN2 mutations in melanoma.Cancer surveys1996; 26: 115–32.
13.
LynchH.T., FusaroR.M., SandbergA.A.. Chromosome instability and the FAMM syndrome.Cancer Genet Cutogenet1993; 71: 27–39.
PathakS., DrwingaH.L., HsuT.C.Involvement of chromosome 6 in rearrangements in human malignant melanoma.Cytogenet Cell Genet1983; 36: 573–9.
16.
TrentJ.M., RosenfeldS.B., MeyskensF.L.Chromosome 6q involvement in human malignant melanoma.Cancer Genet Cytogenet1983; 9: 177–80.
17.
BalabanG.B., HerlynM., ClarkW.H., NowellP.C.Karyotypic evolution in human malignant melanoma.Cancer Genet Cytogenet1986; 19: 113–22.
18.
HechtF., Hecht McCawB.K.Chromosome rearrangements in dysplastic nevus syndrome predisposing to malignant melanoma.Cancer Genet Cytogenet1988; 35: 73–8.
19.
PedersenM.I., WangN.Chromosomal evolution in the progression and metastasis of human malignant melanoma. A multiple lesion study.Cancer Genet Cytogenet1989; 41: 185–201.
20.
SozziG., MiozzoM., CalderoneC.. Chromosome abnormalities and fragile sites in human melanoma.Cancer Genet Cytogenet1990; 66: 61–7.
21.
ZhangJ., TrentJ.M., MeltzerP.S.Utilization of chromosome microdissection for rapid characterization of amplification-units in human cancer: identification of IGF-1R amplification in malignant melanoma. Fifth international workshop on chromosomes in solid tumors - Abstracts.Cancer Genet Cytogenet1993; 66: 149.
22.
Cannon-AlbrightL.A., MeyerL.J., GoldgarD.E.. Penetrance and expressivity of the 9p melanoma susceptibility locus.Cancer Res1994; 54: 6041–4.
23.
PiepkornM.W.Genetic basis of susceptibility to melanoma.J Amer Acad Dermatol1994; 31: 1022–39.
24.
OhtaM.W., NagaiH., ShimizuM.. Rarity or somatic and germline mutations of the cyclin-dependent kinase 4 inhibitor gene, CDK41, in melanoma.Cancer Res1994; 54: 5269–72.
KambA., ShattukeidensD., EelesR.. Anlysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus.Nature Genet1994; 8: 22–6.
27.
FountainJ.W., KaraylorguM., ErnstoffM.S.. Homozygous deletions within human chromosome band 9p21 in melanoma.PNAS1992; 89: 10557–61.
28.
Cannon-AlbrightL.A., GoldarD.E., MeyerL.J.. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22.Science1992; 258: 1148–52.
AckermanA.B., MiharaI.Dysplasia, dysplastic melanocytes, dysplastic nevi, the dysplastic nevus syndrome and the relation between dysplastic nevi and malignant melanomas.Hum Pathol1985; 13: 141–256.
34.
KraemerK.H., TuckerM., TaroneR.. Risk of cutaneous melanoma in dysplastic nevus syndrome types A and B.N Engl J Med1986; 315: 1315–6.
35.
MarghoobA.A., KopfA.W., RigelD.S.. Risks of cutaneous malignant melanoma in patients with classical atypical-mole syndrome. A case-control study.Arch Dermatol1994; 130: 993–8.
36.
SoberA.J., BursteinJ.M.Precursors to skin cancers.Cancer1995; 75: 645–50.
37.
SmithP.J., GreeneM.H., DevlinD.A.. Abnormal sensitivity to UV irradiation in cultured skin fibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome.Int J Cancer1989; 30: 39–45.
38.
GhidoniA., PriviteraE., RaimondiE.. Malignant melanoma: sister chromatid exchange analysis in three families.Cancer Genet Gytogenet1983; 9: 347–54.
39.
IlleniM.T., RoviniD., GrassiC.. Sister chromatid exchange analysis in familial groups of familial melanoma patients.Cancer Genet Cytogenet1991; 53: 237–46.
40.
PereraM.I., UmK.I., GreenM.H.. Hereditary dysplastic nevus syndrome: lymhpoid cell ultraviolet hypermutability in association with increased melanoma susceptibility.Cancer Res1986; 46: 1005–9.
41.
JungE.G., BohnertE., BoonenH.Dysplastic nevus syndrome: ultraviolet hypermutability confirmed in vitro by elevated sister chromatid exchanges.Dermatologia1986; 173: 297–300.
42.
PriviteraE., GhidoniA., RaimondiE.. Sister chromatid exchange and proliferation pattern in stimulated lymphocytes of cutaneous malignant melanoma patients.Cancer Genet Cytogenet1985; 15: 37–45.
43.
SanfordK., TaroneR.E., PrashadR.. Hypersensitivity to G2 chromatid radiation damage in familial dysplastic nevus syndrome.Lancet1987; 2: 1111–6.
44.
CaporasoN., GreeneM.H., TsaiS.. Cytogenetics in hereditary malignant melanoma and dysplastic nevus syndrome: is dysplastic nevus syndrome a chromosomal instability syndrome?Cancer Genet Cytogenet1987; 24: 299–314.
45.
JaspersN.G.J., Roza-de JongE.J.M., DonselaarI.G.Sister chromatid exchanges, hyperdiploidy, and chromosomal rearrangements studied in cells from melanoma-prone individuals belonging to families with dysplastic nevus syndrome.Cancer Genet Cytogenet1987; 24: 33–43.
46.
RothM., BoyleJ.M., MullerH.J.Thymidine dimer repair in fibroblasts of patients with dysplastic nevus syndrome (DNS).Experientia1988; 44: 169–71.
47.
HurlimanA.F., BohnertE., SchnyderU.W., JungE.G.Dysplastic nevus syndrome. Interfamilial identification of carriers by cytogenetics.Dermatology1992; 184: 223–5.
48.
PerryP., WolffS.New Giemsa method for differential staining of sister chromatids.Nature (London)1974; 251: 156–8.
49.
LaundyG.Jr., PeberdyM., KlondaP., BradleyB.A.Application of automated simultaneous double fluorescence (SDF). II. HLA class-I phenotyping using immunogenetically separated T lymphocytes.J Immunogenetics1989; 16: 141–8.
50.
RoviniD., PellegrisG., CascinelliN.. HLA antigens in familial and sporadic cutaneous melanoma.Tumori1988; 74: 657–64.
51.
LambertB., BredbergA., McKenzieW., StenM.Sister chromatid exchange in human population: the effect of smoking, drug treatment and occupational exposure.Cytogenet Cell Genet1982; 33: 62–7.
52.
HollaenderD.H., TockmanM.S., LiangY.W.. SCE in the peripheral blood (lymphocytes) of cigarette smokers and in lung cancer patients, and the effect of chemotherapy.Hum Genet1978; 44: 165–71.
53.
HopkinJ.M., EvansJ.H.Cigarette smoke-induced DNA damage and lung cancer risks.Nature1980; 283: 388–90.
54.
HusumB., NiebuhrH.C.Increased sister chromatid exchange frequency in lymphocytes of healthy cigarette smokers.Hereditas1982; 96: 85–8.
