Melanoma genetics

Read, Jazlyn; Wadt, Karin; Hayward, Nicholas K.

doi:10.1136/jmedgenet-2015-103150

Cited by 192 publications

(198 citation statements)

References 110 publications

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“…Melanoma predisposition is lower in dark-skinned individuals who tan easily and never burn (Fitzpatrick skin types III and IV) than in fair-skinned, blond or red-haired individuals who seldom tan and always burn (Fitzpatrick skin types I and II), suggesting that the genes determining skin colour are the primary genetic determinants of melanoma susceptibility (115,135). This fact is clearly observed in the USA, where European-origin…”

Section: Cutaneous Melanomamentioning

confidence: 67%

“…Although the majority of genetic alterations triggering melanoma development occur as randomly-acquired mutations within melanocytes, the presence of inherited germline variants is an important factor in melanoma susceptibility (115). Melanoma predisposition is lower in dark-skinned individuals who tan easily and never burn (Fitzpatrick skin types III and IV) than in fair-skinned, blond or red-haired individuals who seldom tan and always burn (Fitzpatrick skin types I and II), suggesting that the genes determining skin colour are the primary genetic determinants of melanoma susceptibility (115,135).…”

Section: Cutaneous Melanomamentioning

confidence: 99%

“…According to the epidermal layer of origin, non-melanoma skin cancers can also be subdivided into basal cell carcinoma (BSC) and squamous cell carcinoma (SCC) ( Figure 9). The principal aetiological factors associated with the predisposition to skin cancer include environmental (such as the geographic location and sunlight exposure) and genetic factors (inherited germline variants that influence in pigmentationrelated phenotype diversity) (115,116). Figure 9.…”

Section: Skin Cancermentioning

confidence: 99%

“…The CDKN2A locus codes for two important tumour suppressor proteins, p16 INK4A (p16) and p14 ARF (p14), which are transcribed from different reading frames (115). In response to DNA damage induced by chronic exposure to sunlight, p16 delays cell proliferation through inhibition of cyclindependent kinases 4 and 6 (CDK4 and CDK6) and cyclin D1 (CCND1), thus preventing the phosphorylation of the retinoblastoma protein (Rb) and blocking cell cycle progression from G1 to S phase (115,149). This cell cycle arrest allows cells to repair DNA damage before resuming cell division.…”

Section: Introductionmentioning

confidence: 99%

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The genetic basis of sunlight sensitivity and melanoma-risk pigmentation phenotypes: The role of sex-specific genetic effects, 3' untranslated regions and melanoma susceptibility genes

Fuster¹

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AGRADECIMIENTOSAntes de presentar este trabajo, es momento de agradecer el respaldo de todas aquellas personas que han hecho posible que hoy sea una finisher de esta carrera de larga distancia que es hacer una tesis doctoral.Mis primeras líneas de agradecimiento son para mi director, Conrado Martínez-Cadenas, y co-directora de tesis, Gloria Ribas; quienes con su dedicación, experiencia y profesionalidad me han guiado de manera excepcional durante las diferentes fases de este trabajo, tanto en el proceso puramente experimental como en el análisis, interpretación y presentación de los datos. A Conrado, gracias por darme la oportunidad de realizar la tesis en su grupo de investigación, además de por su apoyo personal, confianza, cercanía y dedicación. Gracias por mover cielo y tierra porque esto fuera posible. A Gloria, gracias por abrirme las puertas de su laboratorio y, sobre todo, por sus excepcionales consejos que, no sólo me han ayudado a desarrollar esta tesis, sino que también han permitido la publicación de los resultados obtenidos.Gracias a Maider Ibarrola-Villava y Maria Peña-Chilet, miembros del grupo de investigación del Departamento de Oncología del INCLIVA, por acompañarme en este largo camino, por su valiosa aportación y su gran compañerismo.Gracias a Zalfa Abdel-Malek por acogerme en su laboratorio y darme la oportunidad de participar en un ambicioso proyecto que ha enriquecido sustancialmente mi carrera investigadora. Gracias por su exigencia y crítica constructiva, pero también por su cariño durante mi estancia. Mención especial a Vicky Sope y Renny Starner por su incalculable ayuda, paciencia y amistad. Gracias de corazón por dejarme empapar de vuestra profesionalidad.Gracias a todo el personal de la Unidad Predepartamental de Medicina de la Universitat Jaume I de Castellón, por el buen humor y compañerismo demostrado. Mención especial para mis compañeros de batalla en el laboratorio. Gracias por esas largas conversaciones y hacerme sentir afortunada por compartir mi trabajo diario con vosotros. Gracias por todo lo compartido.Gracias también a todas esas personas anónimas que voluntariamente han donado una muestra, y al personal médico de los diferentes hospitales encargados de recoger dichas muestras, ya que sin su contribución este trabajo no habría existido.Finalmente, es necesario expresar mi mayor gratitud a todas esas personas que indirectamente también han sido partícipes de este trabajo. A mi familia, por creer en mí.A mi padre, por enseñarme el valor del esfuerzo, el trabajo duro y la disciplina. A mi madre, por enseñarme a tener paciencia. A mi hermana, por ser mi mejor amiga y consejera, especialmente en la estadística y el uso del R. A Manoli, porque todo lo vivido juntas es lo que me ha hecho ser lo que soy. A mi grupo de entrenamiento, por ayudarme a evadirme de todo en los momentos que más lo necesitaba. A Iván, por estar siempre a mi lado. Por no dejarme caer. Por saber cómo hacer que confiara en mi misma. Por hacerme ver que soy una privilegiada hasta en los momentos menos buenos...

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Section: Cutaneous Melanomamentioning

confidence: 67%

Section: Cutaneous Melanomamentioning

confidence: 99%

Section: Skin Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The genetic basis of sunlight sensitivity and melanoma-risk pigmentation phenotypes: The role of sex-specific genetic effects, 3' untranslated regions and melanoma susceptibility genes

Fuster¹

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“…But with the in-depth understanding of the molecular and genetic aspects of melanoma during the recent decades, researchers find that several "driver" mutations are closely associated with the disease progression, prognosis and tumorigenesis [1, [5][6][7]. Melanoma arises when mutations of these cancer driver genes accumulate and alter the melanocyte cell proliferation, programmed death and differentiation.…”

Section: Major Genetic Recurrent Driver Mutations Of Melanomamentioning

confidence: 99%

Discovery of Novel Tubulin Polymerization Inhibitors and Survivin Inhibitors as Potential Anticancer Agents

Xiao¹

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Improvement of Genetic Testing for Cutaneous Melanoma in Countries With Low to Moderate Incidence

et al. 2017

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IMPORTANCE Genetic testing for melanoma-prone mutation in France, a country with low to moderate incidence of melanoma, is proposed in cases with 2 invasive cutaneous melanomas and/or related cancers in the same patient, or in first-or second-degree relatives (rule of 2). In preclinical studies, these rules led to disclosure of mutation(s) in more than 10% of these families, the threshold widely accepted to justify genetic testing for cancers.OBJECTIVE To reconsider these criteria in a general population testing of patients. DESIGN, SETTING, AND PARTICIPANTSThis was a retrospective study, performed from 2004 to 2015 at Angers and Lyons University Hospitals, of a cohort of 1032 patients who underwent genetic testing. MAIN OUTCOMES AND MEASURESFrequency of mutation in high (CDKN2A, CDK4, and BAP1) and intermediate (MITF) susceptibility genes; statistical effect of histologic subtype, age, dysplastic nevi syndrome, and associated cancers on mutation rate; and evaluation of cases with anamnestic uncertainty. RESULTSThe mutation rate was 67 of 1032 patients (6.5%). Their mean (SD) age was 54.5 (14.2) years [range, 18-89 years], and 543 (52.6%) were men. It increased to 38 of 408 patients (9.3%) when applying a rule of 3 (those with Ն3 primary melanomas or genetically related cancers) (P = .68) and to 27 of 150 patients (18.0%) with a rule of 4 (4 primary melanomas or related cancer) (P < .001). The impact of age at first melanoma was observed only in those younger than 40 years, with a rate of 32 of 263 (12.1%) (P = .12) for the rule of 2 and 22 of 121 (18.2%) (P = .001) for the rule of 3. Use of the rule of 2 in patients younger than 40 years reduced the number of missed CDKN2A-mutated-families when applying the rule of 3 from 14 of 43 to 7 of 43. Anamnestic uncertainty, found in 88 families (8.5%), if excluded, would have led us to withdraw of only 21 cases (23.8%), and only 1 mutation would have been missed. CONCLUSIONS AND RELEVANCEWe propose using the rule of 3 to recommend genetic testing in France and countries with low to moderate incidence of melanoma, except in families and patients with a first melanoma occurrence before age 40 years in whom the rule of 2 could be maintained.

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Melanoma genetics

Cited by 192 publications

References 110 publications

The genetic basis of sunlight sensitivity and melanoma-risk pigmentation phenotypes: The role of sex-specific genetic effects, 3' untranslated regions and melanoma susceptibility genes

The genetic basis of sunlight sensitivity and melanoma-risk pigmentation phenotypes: The role of sex-specific genetic effects, 3' untranslated regions and melanoma susceptibility genes

Discovery of Novel Tubulin Polymerization Inhibitors and Survivin Inhibitors as Potential Anticancer Agents

Improvement of Genetic Testing for Cutaneous Melanoma in Countries With Low to Moderate Incidence

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