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Pigment Cell & Melanoma Research

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https://www.readbyqxmd.com/read/28097822/synthetic-lethality-emerging-targets-and-opportunities-in-melanoma
#1
REVIEW
Nicola Thompson, David Adams, Marco Ranzani
Great progress has been made in the treatment of melanoma through use of targeted therapies and immunotherapy. One approach that has not been fully explored is synthetic lethality, which exploits somatically acquired changes, usually driver mutations, to specifically kill tumour cells. We outline the various approaches that may be applied to identify synthetic lethal interactions and define how these interactions may drive drug discovery efforts. This article is protected by copyright. All rights reserved.
January 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28097802/genomic-analysis-and-clinical-management-of-adolescent-cutaneous-melanoma
#2
Roy Rabbie, Mamun Rashid, Ana M Arance, Marcelo Sánchez, Gemma Tell-Marti, Miriam Potrony, Carles Conill, Remco van Doorn, Stefan Dentro, Nellele A Gruis, Pippa Corrie, Vivek Iyer, Carla Daniela Robles-Espinoza, Joan A Puig-Butille, Susana Puig, David J Adams
Melanoma in young children is rare, however its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease four years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas, and 275 adult cutaneous melanomas. A somatic BRAF(V)(600E) mutation and a high mutational load equivalent to that found in adult melanoma, and composed primarily of C>T mutations was observed...
January 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28024115/mutation-load-in-melanoma-is-affected-by-mc1r-genotype
#3
Peter A Johansson, Antonia Pritchard, Ann-Marie Patch, James S Wilmott, John V Pearson, Nicola Waddell, Richard A Scolyer, Graham J Mann, Nicholas K Hayward
Whole-genome sequencing of matched germline and tumour pairs in a well characterised cohort of melanoma patients allowed investigation of associations between melanoma body site, age at melanoma onset and MC1R variant status with overall mutation burden and specific base pair changes observed in the corresponding melanoma. We observed statistically significant associations between mutation burden in melanoma and body site, age at onset and MC1R genotype, for both ultraviolet radiation (UVR) signature changes (C>T and CC>TT) and non-UVR base pair substitutions, as well as with overall variant load...
December 26, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28024114/evaluation-of-tubulin-%C3%AE-3-as-a-novel-senescence-associated-gene-in-melanocytic-malignant-transformation
#4
Kyriakos Orfanidis, Petra Wäster, Katarzyna Lundmark, Inger Rosdahl, Karin Öllinger
Malignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies...
December 26, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28002643/clinical-and-therapeutic-implications-of-braf-mutation-heterogeneity-in-metastatic-melanoma
#5
Nima Mesbah Ardakani, Connull Leslie, Fabienne Grieu-Iacopetta, Wei-Sen Lam, Charley Budgeon, Michael Millward, Benhur Amanuel
Heterogeneity of BRAF mutation in melanoma has been a controversial subject. Quantitative data on BRAF allele frequency (AF) is sparse and the potential relationship with response to BRAF inhibitors (BRAFi) in patients with metastatic melanoma is unknown. We quantitatively measured BRAF AF in a cohort of treatment naïve metastatic melanoma samples by pyrosequencing and correlated with survival data in patients treated with BRAFi as part of their clinical care. 52 samples from 50 patients were analysed. BRAF V600E mutations were detected in 71...
December 21, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27977907/an-ongoing-role-for-wnt-signaling-in-differentiating-melanocytes-in-vivo
#6
Laura Vibert, Gerardo Aquino, Ines Gehring, Tatiana Subkhankulova, Thomas F Schilling, Andrea Rocco, Robert N Kelsh
A role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, but possible ongoing roles in melanocyte differentiation have received little attention. Using a systems biology approach to investigate the gene regulatory network underlying stable melanocyte differentiation in zebrafish highlighted a requirement for a positive feedback loop involving the melanocyte master regulator Mitfa. Here we test the hypothesis that Wnt signaling contributes to that positive feedback...
December 15, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27930879/melanoma-exosomes-deliver-a-complex-biological-payload-that-upregulates-ptpn11-to-suppress-t-lymphocyte-function
#7
Yueting Wu, Wentao Deng, Emily Chambers McGinley, David J Klinke
As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27930874/tert-promoter-mutations-associate-with-mc1r-variants-in-melanoma-patients
#8
LETTER
Eduardo Nagore, Diana Reyes-Garcia, Barbara Heidenreich, Zaida Garcia-Casado, Celia Requena, Rajiv Kumar
Mutations in the promoter of the telomerase reverse transcriptase gene (TERT) are one of the most prevalent somatic alterations in melanomas that occur at early stages of the disease (Heidenreich et al., 2014; Horn et al., 2013; Shain et al., 2015). Those mutations increase TERT expression by creating new binding motifs for Ets transcription factors which ultimately increase telomerase activity (Horn et al., 2013). Moreover, melanomas harbouring TERT promoter mutations display aggressive characteristics and associate with worse disease-free and melanoma-specific survival, particularly in presence of the BRAF or NRAS mutations (Griewank et al...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27930866/phylloid-hypomelanosis-associated-with-a-mosaic-trisomy-13-in-the-13q31-3-qter-region-atypical-phylloid-distribution-and-typical-hypomelanosis
#9
LETTER
Naoki Oiso, Kazuko Sakai, Kazuto Nishio, Akira Kawada
Mosaicism in human skin results in different cutaneous patterns: the narrow lines of Blaschko (type 1a), the broad lines of Blaschko (type 1b), the checkerboard pattern (type 2), the phylloid pattern (type 3), and a patchy pattern without midline separation (type 4) (Happle, 1993). The phylloid pattern is characterized by an arrangement of pigmentary disturbances reminiscent of floral ornamentsor a Jugendstil painting (Happle, 1993). Phylloid hypomelanosis is characterized by congenital hypopigmented macules following the phylloid pattern...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27930864/tert-promoter-mutations-are-not-always-associated-with-poor-prognosis-in-atypical-spitzoid-tumors
#10
LETTER
Celia Requena, Barbara Heidenreich, Rajiv Kumar, Eduardo Nagore
The differential diagnosis between benign and malignant lesions in the field of spitzoid tumors can often be a challenge, and in some cases almost impossible. Significance of this differential diagnosis is due to its clinical implications; an erroneous diagnosis of spitzoid melanoma for a Spitz nevus can result in unnecessary treatment, which would not be required in the latter case. In recent years, diagnosis of atypical spitzoid tumor is preferred for lesions with features between benign and unequivocally malignant tumors...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27893188/dek-oncogene-is-overexpressed-during-melanoma-progression
#11
Erica Riveiro-Falkenbach, Yolanda Ruano, Rosa M García-Martín, David Lora, Metehan Cifdaloz, Francesco Acquadro, Claudio Ballestin, Pablo L Ortiz-Romero, María S Soengas, José L Rodríguez-Peralto
DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions...
November 28, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27885826/posterior-reversible-encephalopathy-syndrome-due-to-combination-vemurafenib-and-cobimetinib-for-metastatic-melanoma
#12
LETTER
F Boukari, P M Dugourd, M Chassang, L Mondot, T Passeron, J P Lacour, H Montaudie
The combination of BRAF and MEK inhibitors has improved the prognosis of patients with BRAFV600-mutated metastatic melanoma (Larkin et al., 2014). The toxicity profiles of these drugs are mostly defined by gastrointestinal events, photosensitivity, hepatitis, and arthralgia (Larkin et al., 2014). We report a case of posterior reversible encephalopathy syndrome (PRES) induced by vemurafenib and cobimetinib. A 68-year-old man, with neither a medical history nor any treatment, was surgically treated in November 2015 for stage IIB chest melanoma (superficial-spreading melanoma, Breslow 7 mm, with a high mitotic rate and without ulceration)...
November 25, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27864876/kinase-gene-fusions-in-defined-subsets-of-melanoma
#13
Jacqueline Turner, Kasey Couts, Jamie Sheren, Siriwimon Saichaemchan, Witthawat Ariyawutyakorn, Izabela Avolio, Ethan Cabral, Magdelena Glogowska, Carol Amato, Steven Robinson, Jennifer Hintzsche, Allison Applegate, Eric Seelenfreund, Rita Gonzalez, Keith Wells, Stacey Bagby, John Tentler, Aik-Choon Tan, Joshua Wisell, Marileila Varella-Garcia, William Robinson
Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in-situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1...
November 19, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27864868/repigmentation-in-vitiligo-position-paper-of-the-vitiligo-global-issues-consensus-conference-vgicc
#14
Emily Yiping Gan, Viktoria Eleftheriadou, Samia Esmat, Iltefat Hamzavi, Thierry Passeron, Markus Böhm, Tag Anbar, Boon Kee Goh, Cheng-Che Eric Lan, Harvey Lui, M Ramam, Noufal Raboobee, Ichiro Katayama, Tamio Suzuki, Davinder Parsad, Vaneeta Seth, Henry W Lim, Nanja van Geel, Sanjeev Mulekar, John Harris, Richard Wittal, Laila Benzekri, Yvon Gauthier, Prasad Kumarasinghe, Steven Tien Guan Thng, Caio Cesar Silva de Castro, Marwa Abdallah, Charlotte Vrijman, Marcel Bekkenk, Julien Seneschal, Amit G Pandya, Khaled Ezzedine, Mauro Picardo, Alain Taïeb
The Vitiligo Global Issues Consensus Conference (VGICC), through an international e-Delphi consensus, concluded that "repigmentation" and "maintenance of gained repigmentation" are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation and the second summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over three years...
November 19, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27863059/study-of-the-comparative-expression-of-cxcl9-cxcl10-and-ifn%C3%AE-in-vitiligo-and-alopecia-areata-patients
#15
LETTER
Amal Maouia, Laura Sormani, Monia Youssef, Ahmed Noureddine Helal, Asma Kassab, Thierry Passeron
Vitiligo and Alopecia areata (AA) are autoimmune T cell-mediated diseases of the skin that share the implication of the IFNγ pathway in their pathophysiology. C-X-C motif chemokine receptor 3 (CXCR3) and its ligands, C-X-C motif chemokine ligand 9 (CXCL9), CXCL10 and CXCL11, are linked to the Th1 pattern and have been suggested as one of the most relevant chemokine axes that promote T cell migration in different autoimmune and inflammatory processes (Lacotte et al., 2009). Chemokines play an important role in regulating the homing of immune cells (Vazirinejad et al...
November 12, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27863034/abstracts
#16
(no author information available yet)
No abstract text is available yet for this article.
November 12, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27863085/pharmacokinetics-of-dabrafenib-in-a-patient-with-metastatic-melanoma-undergoing-haemodialysis
#17
John J Park, Alan V Boddy, Xiaoman Liu, David Harris, Vincent Lee, Richard F Kefford, Matteo S Carlino
The combination of dabrafenib and trametinib is a standard of care for the management of BRAF mutant metastatic melanoma. Clinical trials excluded patients with end-stage kidney disease (ESKD) and as such no data are available regarding the safety, efficacy and pharmacokinetics of these drugs in such patients. Here, we present the case of a 78 year-old male patient with ESKD managed with haemodialysis (HD), treated with dabrafenib and trametinib at reduced doses. The patient has had a partial response, and this response continues at 9 months since our last follow up without any dose escalation...
November 10, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27863025/decision-to-grow-or-to-invade-is-at-the-flick-of-metabolic-switch-pgc1%C3%AE
#18
Kristen S Hill, Minjung Kim
Cancer cells constantly reprogram their metabolism to meet anabolic and catabolic demands in real time. Increased aerobic glycolysis (the Warburg effect) is associated with highly proliferative tumors, since it confers several advantages to proliferating tumor cells by providing rapid ATP production from glycolysis and macromolecules (building blocks) for cell division. On the other hand, mitochondria-dependent oxidative phosphorylation (OxPhos) generates the maximal amount of ATP from glucose. Although underappreciated, OxPhos is also utilized to support growth of cancer cells, especially for "oxidative tumors" such as lymphomas, glioblastomas, and melanomas...
November 10, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27804239/response-to-the-commentary-on-a-genomewide-association-study-in-caucasian-women-suggests-the-involvement-of-hla-gene-in-the-severity-of-facial-solar-lentigines
#19
LETTER
Vincent Laville, Sigrid Le Clerc, Khaled Ezzedine, Jean-François Zagury
No abstract text is available yet for this article.
November 2, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27804227/reduce-reuse-recycle-a-retrieval-transport-pathway-for-the-membrane-fusion-machinery-involved-in-melanosome-biogenesis
#20
Jarred J Bultema, Santiago M Di Pietro
The formation of the melanosome - the organelle responsible for synthesizing the melanin pigment found in hair, skin, and eyes - has long been studied as a model for the specialized development of organelles. In part this is due to the relative ease in identifying genes that impact pigmentation based on subtle to severe forms of albinism. The melanosome belongs to a family of lysosome-related organelles (LROs) that share some characteristics including an acidic lumen, part of their protein content, and biogenesis mechanisms...
November 2, 2016: Pigment Cell & Melanoma Research
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