Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the UV effect on epidermal melanocytes, 21 volunteers and 11 patients with dysplastic nevus syndrome (DNS) received UVB irradiation three times weekly during 17 days. Skin biopsies were taken before and three weeks after the last irradiation (on day 37) from exposed and covered buttock skin. The epidermal melanocyte population density was estimated in dopa-stained split skin preparations. The biopsies taken on day 37 revealed that repeated UVB irradiation induces an increase in the number of melanocytes not only in exposed but also in covered skin. This increased mitotic activity might be a link between sun exposure and melanoma development in covered skin. The size of the proliferative response was inversely correlated to the basal melanocyte number. The larger population increase in skin with few melanocytes might amplify the propagation of DNA damage and increase the likelihood of tumor development. The pigment metabolite 5-S-cysteinyldopa (5-S-CD) was measured in urine before the irradiation and twice weekly until day 38. No correlation was found between the basal 5-S-CD excretion and the size or activity of the melanocyte organ, suggesting that the basal 5-S-CD excretion is mainly of non-melanocytic origin. Despite numerous nevi, DNS-patients did not differ from controls in their 5-S-CD excretion. The normal upper range for the tumor maker 5-S-CD is therefore valid in these melanoma-prone subjects. During the irradiation, subjects with a low tanning ability developed a more pronounced erythema and excreted more 5-S-CD than those with a good tanning ability. This suggests that the UVB-induced 5-S-CD excretion is rather due to melanocyte damage than to an increased melanin synthesis. To investigate the influence of sun exposure on the development of nevi and melanoma (CMM), the distribution over the body surface of CMM, common nevi (CN) greater than or equal to 2 mm and dysplastic nevi (DN) was registered in 121 melanoma patients and 310 controls. Four times as many nevi were found in a sun-exposed area than in a comparable sun-protected area, demonstrating that sun exposure plays an important role in nevus development. Subjects with DNA had a larger difference in nevus counts between the two areas than subjects without DN, indicating a different UV-dose and/or a higher sensitivity to the "nevogenic" effect of UV-light than subjects without DN.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Melanocytes, moles and melanoma--a study on UV effects. 181 38

We report seven examples of pigmented spindle cell naevus (PSCN) and variants, emphasizing their histopathologic differentiation from malignant melanoma (CMM). Confusion with CMM may occur because of upward migration (pagetoid spread) of cells, prominent lateral extension of lentiginous melanocytic hyperplasia, and cytological atypia in spindle cell naevi. However, these proliferations are usually associated with a symmetrical and orderly growth pattern, confinement of the pagetoid spread to the lower epidermis, 'maturation' of the dermal component, and lack of marked cytological atypia.
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PMID:Pigmented spindle cell naevus and its variants: distinction from melanoma. 261 Nov 23

Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area. The occurrence of a shared high-risk haplotype in six of the families strongly suggests a founder effect in the Leiden region. No indication for locus heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a general tumour suppressor gene predisposing not only to melanoma but also to other malignancies. Interestingly, the occurrence of apparent clinical FAMMM cases with melanoma but without the high-risk deletion haplotype suggests the necessity of additional (naevus) genes to explain the complete FAMMM phenotype.
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PMID:CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families. 764 May 18

We report three patients with the atypical mole syndrome (AMS) [also known as dysplastic naevus or FAMMM syndrome] who presented with primary acquired melanosis (PAM). PAM is a melanocytic lesion of the conjunctiva which may progress to conjunctival melanoma. The association of this rare condition with the AMS phenotype in three individuals suggests that PAM may be a conjunctival manifestation of the AMS.
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PMID:Three cases of primary acquired melanosis of the conjunctiva as a manifestation of the atypical mole syndrome. 842 27

Consensus was recently reached in the Netherlands regarding the clinical management of dysplastic naevi and the definitions in clinical and pathological diagnostics. The term 'dysplastic' is reserved for histological diagnostics; the term preferred for clinical use is 'clinically atypical naevus'. A naevus is defined as clinically atypical if it meets three of the following five criteria: > or = 5 mm in diameter, vaguely bordered, asymmetrically shaped, irregularly pigmented and a red hue (erythema). Presence of clinically atypical naevi is a main risk factor for melanoma. Dysplastic naevus syndrome (DNS) is present if a patient has a melanoma and one or several clinically atypical naevi. The diagnosis of 'familial DNS' (familial atypical multiple mole-melanoma syndrome, abbreviation FAMMM syndrome) is made if at least two close relatives (including the patient) are known with a melanoma with or without atypical naevi, while one or several (other) relatives have atypical naevi. The risk of melanoma in a gene carrier of familial DNS is close to 100%, while multiple melanomas develop in 30% of the gene carriers. No DNA diagnostics is yet possible in most DNS/FAMMM families, because of the involvement of genes yet unknown. Accordingly, at present it is still too early for DNA diagnostics. Currently, therefore, the diagnosis is based only on anamnestic, clinical and histological grounds.
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PMID:[Dysplastic nevi and the risk of melanoma: a guideline for patient care. Nederlandse Melanoom Werkgroep van de Vereniging voor Integrale Kankercentra]. 955 Jul 52

Oncologists who are aware of the progress in hereditary cancer syndrome diagnosis, and, in particular, of how this effort may be effectively facilitated through a comprehensive family history in concert with molecular genetic studies, are in the envious position of designing highly targeted screening and management programs for the membership of these cancer-prone families. The Lynch syndrome is discussed as a clinical model wherein the presence of mismatch repair mutations provides a high level of diagnostic certainty for the initiation of targeted cancer screening and management. The familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome, on the other hand, provides another model with cancer-control potential. Given its phenotypic features of multiple atypical nevi, high total body mole count and cutaneous malignant melanoma, coupled with the integral association of PC in a subset of FAMMM kindreds with the CDKN2A germline mutation, this may result in a perhaps lower level of diagnostic certainty when compared with the Lynch syndrome. This knowledge may impact upon progress in the earlier diagnosis of melanoma and provide an impetus for creative diagnostic methods in PC, a disease that, at this time, demonstrates a mortality rate virtually identical to its incidence rate.
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PMID:Hereditary cancer syndrome diagnosis: molecular genetic clues and cancer control. 1738 17

Some cases of pancreatic cancer (PC) are described to cluster within families. With the exception of PALLD gene mutations, which explain only a very modest fraction of familial cases, the genetic basis of familial PC is still obscure. Here the literature was reviewed in order to list the known genes, environmental factors, and health conditions associated with PC or involved in the carcinogenesis of the pancreas. Most of the genes listed are responsible for various well-defined cancer syndromes, such as CDKN2A (familial atypical mole-multiple melanoma, FAMMM), the mismatch repair genes (Lynch Syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and BRCA2 (breast-ovarian familial cancer), where PC is part of the cancer spectrum of the disease. In addition, in this review I ranked known/possible risk factors extending the analysis to the hereditary pancreatitis (HP), diabetes, or to specific environmental exposures such as smoking. It appears that these factors contribute strongly to only a small proportion of PC cases. Recent work has revealed new genes somatically mutated in PC, including alterations within the pathways of Wnt/Notch and DNA mismatch repair. These new insights will help to reveal new candidate genes for the susceptibility to this disease and to better ascertain the actual contribution of the familial forms.
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PMID:Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature. 1915 Apr 14

Families with both melanoma and pancreatic cancer are extremely rare and some are affected with the autosomal dominant inherited familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome. The phenotypic and genotypic expressions of such pancreatic cancer-melanoma prone families are not well defined. The National Case Collection of Familial Pancreatic Cancer of the Deutsche Krebshilfe includes 110 pancreatic cancer families, 18 of which (16%) show an association of pancreatic cancer and melanoma. These 18 families were analysed regarding their phenotype and the prevalence of germline mutations in the candidate genes CDKN2A, BRCA2, CHEK2, NOD2, ARL11 and Palladin (PALLD). There were two types of families: five families with the FAMMM-PC phenotype and 13 PC/melanoma families without the multiple mole phenotypes (PCMS). The prevalences of PC and melanoma in the two types of families were similar. The prevalence of other tumour types, especially breast carcinoma, was higher (11%) in PCMS- than in FAMMM-PC families (2.4%, p = 0.02). CDKN2A mutations were identified in 2 of 18 (11%) PCMS families. A cosegregating BRCA2 mutation was detected in one PCMS family without breast cancer. None of the reported germline mutations in the NOD2, Palladin, ARL11 or CHEK2 genes were detected in either type of family. In conclusion, families with an accumulation of PC and melanoma show a large variety of phenotypic expression, which is not always consistent with the FAMMM-PC phenotype. More PC/melanoma-prone families need to be analysed to clarify whether such families represent variations of the FAMMM-PC syndrome or two distinct hereditary cancer syndromes.
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PMID:Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families. 2004 85