Disease relevance of CMM

• The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM [1].
• Uveal malignant melanoma (UMM) also occurs in a familial setting, or sometimes in association with familial or sporadic CMM [2].
• There was, however, a statistically significant difference in age-adjusted median numbers of nevi (P =.004), and CMM case subjects from CDKN2A families without pancreatic cancer had greater numbers of nevi [3].
• Expression of RASEF, a known gene in this region, was examined in tumor tissue from 10 sporadic CMM lesions and was found to be decreased in 70% of these tumors compared with RASEF expression in a human reference RNA pool from 10 different cell types and in 10 breast tumors [4].
• We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 399 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count [5].

Psychiatry related information on CMM

• The relationship between dietary habits and subsequent risk of cutaneous malignant melanoma (CMM) was studied in 25,708 men and 25,049 women aged 16-56 years attending a Norwegian health screening in 1977-1983 [6].
• There is, thus, a need for large prospective studies on the development of CMM and naevi, ideally in different contexts as concerns host factors, sun exposure, and other life-style habits within and across different populations [7].
• CMM was also directly predictive of PTSD symptoms, but not depression symptoms in adulthood [8].
• CONCLUSIONS: Findings support both direct and mediational effects of social resources on adult depression and PTSD symptoms in women with histories of CMM, suggesting that resources are key factors in psychological adjustment of CMM victims [8].

High impact information on CMM

• Moreover, germline mutations identified in some melanoma-prone kindreds last year suggested that CDKN2 is identical to the 9p21-linked melanoma susceptibility gene (MLM); however, failure to identify p16 mutations in all melanoma kindreds putatively linked to 9p21 left some doubts [9].
• Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p [10].
• We used molecular genetic techniques and multipoint linkage analyses to locate the gene responsible for cutaneous malignant melanoma-dysplastic nevus [10].
• The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation [11].
• Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of CMM, which suggests that DNA repair capacity (DRC) plays a role in sunlight-induced CMM in the general population as well [12].

Chemical compound and disease context of CMM

• Immunohistochemical analysis of the N-ras p21 and the p53 proteins was carried out on formalin-fixed sections of naevi, primary melanomas and metastases from patients with sporadic melanoma (SCMM) and with hereditary melanoma (HCMM)/dysplastic naevus syndrome (DNS) [13].
• Two series of cutaneous malignant melanoma (CMM), one from a low incidence area (the Oxford Region) and one from a high incidence area (Western Australia), were compared by one pathologist using the same histological criteria [14].
• The frequency of melanoma (CMM), and of common and dysplastic naevi (CN and DN) in areas of skin chronically, intermittently and rarely exposed to UV light was investigated in 121 melanoma patients (30-50 years) and 310 controls [15].
• Structure of the capsular polysaccharide from Alteromonas sp. CMM 155 [16].
• BACKGROUND: Matrix metalloproteases (MMPs), enzymes with the ability to degrade the extracellular matrix, play an important role in tissue invasion by cutaneous malignant melanoma (CMM) [17].

Biological context of CMM

• Germline mutations at this locus increase susceptibility to cutaneous malignant melanoma (CMM) [18].
• Mutations, loss of heterozygosity and deletions of the CDKN2 locus have been reported in sporadic and familial cutaneous malignant melanomas (CMM) [19].
• To investigate the role of the alterations of p16 expression in melanoma, we evaluated by immunohistochemistry the p16 expression and cell proliferation in 79 primary CMM and 10 benign melanocytic nevi (BMN) [19].
• Considerable controversy exists over the possible assignment of a cutaneous malignant melanoma/dysplastic nevus gene, designated CMM, to the distal short arm of chromosome 1, linked to the PND and D1S47 loci [20].
• No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed [21].

Anatomical context of CMM

• Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM) [1].
• The purpose of this report is to describe the potential diagnostic difficulties created by benign NCAs within the thymus of a 32-year-old man with dysplastic nevus syndrome and malignant melanoma involving mediastinal lymph nodes and the right lung [22].
• Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus type 1 (HSV-1) has been determined in skin fibroblasts from the following hereditary cancer-prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel-Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high incidence of breast and ovarian cancer [23].
• BACKGROUND: Previous studies suggest that the familial atypical multiple-mole melanoma (FAMMM) syndrome may predispose affected families to nonmelanoma carcinomas, including adenocarcinoma of the pancreas [24].
• When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses [25].

Associations of CMM with chemical compounds

• Most of them were identified in sporadic CMM (six in codon 148 Ala/Thr, 12 in codon 84 Asp/Asp and six in 3'UTR) [26].
• These findings provide additional evidence that tumor progression in CMM is associated with changes in integrin phenotypes which include the alpha 3/beta 1 heterodimer [27].
• The most important, and consistent morphological difference was the greater thickness of tumours from the Oxford Region, which is thought to be consistent with the theory that CMM is diagnosed at an earlier stage in high incidence areas because of greater medical and public awareness of the condition [14].
• We found a significant inverse association between vitamin A intake and CMM risk [28].
• The probability of CMM significantly increased with the degree of relative clustering of CN (p less than 0.05) and of DN (p less than 0.01) [15].

Regulatory relationships of CMM

• A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR [21].
• In this study we have investigated whether two single nucleotide polymorphisms (SNPs) in the ICAM-1 gene encoding amino acid substitutions in codons 241 and 469 of the expressed ICAM-1 molecule are associated with susceptibility to and markers of prognosis (including tumour Breslow thickness) in CMM [29].

Other interactions of CMM

• CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein [1].
• Carriers of the p16-Leiden deletion in Dutch families with FAMMM show an increased risk of melanoma when they also carry MC1R variant alleles [30].
• We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer [21].
• These data suggest that among persons with hair colors traditionally associated with increased risk for melanoma, absence of both GSTM1 and GSTT1 may act to further elevate CMM risk [31].
• Exclusion of the familial melanoma locus (MLM) from the PND/D1S47 and MYCL1 regions of chromosome arm 1p in 7 Australian pedigrees [20].

Analytical, diagnostic and therapeutic context of CMM

• Findings from a case-control study of cutaneous malignant melanoma (CMM) in Queensland, Australia, suggest that melanomas exhibiting p53 immunostaining possess different risk factors from those of other melanomas [32].
• METHODS: We conducted a hospital-based case-control study of DRC and CMM among 312 non-Hispanic white CMM patients who had no prior chemotherapy or radiation therapy, and 324 cancer-free control subjects who were frequency-matched to case patients on age, sex, and ethnicity [12].
• 14 patients who developed cutaneous malignant melanoma (CMM) after renal transplantation were studied [33].
• PURPOSE: To assess prospectively the accuracy of 2-[l8F]-2-deoxy-D-glucose positron emission tomography (FDG-PET) for predicting regional node involvement in cutaneous malignant melanoma (CMM) [34].
• PATIENTS AND METHODS: Twenty-three patients with CMM (primary lesions > 1.5 mm thick) scheduled for lymph node dissection (LND) were preoperatively studied with FDG-PET [34].

References