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REVIEW
Eva R Shteinman, James S Wilmott, Ines Pires da Silva, Georgina V Long, Richard A Scolyer, Ismael A Vergara
Aneuploidy, the state of the cell in which the number of whole chromosomes or chromosome arms becomes imbalanced, has been recognized as playing a pivotal role in tumor evolution for over 100 years. In melanoma, the extent of aneuploidy, as well as the chromosomal regions that are affected differ across subtypes, indicative of distinct drivers of disease. Multiple studies have suggested a role for aneuploidy in diagnosis and prognosis of melanomas, as well as in the context of immunotherapy response. A number of key constituents of the cell cycle have been implicated in aneuploidy acquisition in melanoma, including several driver mutations...
2022: Frontiers in Oncology
#22
REVIEW
Alexander H R Varey, Gabrielle J Williams, Serigne N Lo, Cecilia Y Taing, Andrea Maurichi, Mario Santinami, Richard A Scolyer, John F Thompson
Little guidance is currently available for managing patients with melanocytic tumours of uncertain or low malignant potential (MelTUMPs, including melanocytomas), in particular the optimal excision margins and whether to offer sentinel node biopsy (SNB). The objective of this review was to evaluate excision margins and the prognostic utility of SNB by systematic review of the literature and meta-analysis. PRISMA guidelines were followed. Medline, EMBASE and Cochrane databases were searched to October 2021 for studies of patients with MelTUMPs reporting excision margins and/or SNB-positivity...
May 2023: Journal of the European Academy of Dermatology and Venereology: JEADV
#23
EDITORIAL
Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K Mishra, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J DeBerardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L McQuade
PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI). EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts...
January 4, 2023: Clinical Cancer Research
#24
JOURNAL ARTICLE
Rebecca C Simpson, Erin R Shanahan, Marcel Batten, Irene L M Reijers, Mark Read, Ines P Silva, Judith M Versluis, Rosilene Ribeiro, Alexandra S Angelatos, Jian Tan, Chandra Adhikari, Alexander M Menzies, Robyn P M Saw, Maria Gonzalez, Kerwin F Shannon, Andrew J Spillane, Rebecca Velickovic, Alexander J Lazar, Ashish V Damania, Aditya K Mishra, Manoj Chelvanambi, Anik Banerjee, Nadim J Ajami, Jennifer A Wargo, Laurence Macia, Andrew J Holmes, James S Wilmott, Christian U Blank, Richard A Scolyer, Georgina V Long
The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States...
November 2022: Nature Medicine
#25
JOURNAL ARTICLE
Felicity Newell, Peter A Johansson, James S Wilmott, Katia Nones, Vanessa Lakis, Antonia L Pritchard, Serigne N Lo, Robert V Rawson, Stephen H Kazakoff, Andrew J Colebatch, Lambros T Koufariotis, Peter M Ferguson, Scott Wood, Conrad Leonard, Matthew H Law, Kelly M Brooks, Natasa Broit, Jane M Palmer, Kasey L Couts, Ismael A Vergara, Georgina V Long, Andrew P Barbour, Omgo E Nieweg, Brindha Shivalingam, William A Robinson, Jonathan R Stretch, Andrew J Spillane, Robyn P M Saw, Kerwin F Shannon, John F Thompson, Graham J Mann, John V Pearson, Richard A Scolyer, Nicola Waddell, Nicholas K Hayward
Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation, uveal melanoma occurs in the eyes, mucosal melanoma in internal mucous membranes, and acral melanoma on the palms, soles and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNAseq for subsets of tumors. Uveal melanoma is genomically distinct from other melanoma subtypes, harboring the lowest tumor mutation burden and with significantly mutated genes in the G-protein signaling pathway...
September 13, 2022: Cancer Discovery
#26
JOURNAL ARTICLE
Mathias Seviiri, Richard A Scolyer, D Timothy Bishop, Julia A Newton-Bishop, Mark M Iles, Serigne N Lo, Johnathan R Stretch, Robyn P M Saw, Omgo E Nieweg, Kerwin F Shannon, Andrew J Spillane, Scott D Gordon, Catherine M Olsen, David C Whiteman, Maria Teresa Landi, John F Thompson, Georgina V Long, Stuart MacGregor, Matthew H Law
BACKGROUND: The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood. OBJECTIVE: To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS. METHODS: We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis...
September 5, 2022: Journal of Translational Medicine
#27
JOURNAL ARTICLE
Anna K Lawless, David J Coker, Serigne N Lo, Tasnia Ahmed, Richard A Scolyer, Sydney Ch'ng, Omgo E Nieweg, Kerwin Shannon, Andrew Spillane, Jonathan R Stretch, John F Thompson, Robyn P M Saw
No abstract text is available yet for this article.
August 22, 2022: Annals of Surgical Oncology
#28
JOURNAL ARTICLE
Robert V Rawson, Eva R Shteinman, Sameera Ansar, Ismael A Vergara, John F Thompson, Georgina V Long, Richard A Scolyer, James S Wilmott
High expression of PRAME (PReferentially expressed Antigen in MElanoma) and p53 (a proposed marker of desmoplastic melanoma) and low expression of 5-hydroxymethylcytosine (5-hmC) have each been reported in melanoma. However, their combined diagnostic utility for distinguishing melanomas, including uncommon variants, from histological mimics is unknown. This study sought to determine the utility of PRAME, p53 and 5-hmC immunostains for diagnosing melanocytic tumours. A total of 333 cutaneous melanocytic tumours (melanoma n=280, naevi n=53), 20 cutaneous neurofibromas, and 15 scars were evaluated using multiplex immunofluorescence (n=313) or single-plex chromogenic immunohistochemical staining (n=55)...
December 2022: Pathology
#29
JOURNAL ARTICLE
Jessica S Crystal, John F Thompson, John Hyngstrom, Corrado Caracò, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Elisabetta Pennacchioli, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Alexander van Akkooi, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Rogerio I Neves, Carlo Riccardo Rossi, John M Kane, Steven Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy C Hsueh, Alastair MacKenzie-Ross, Mark Kelley, Patrick Terheyden, Tara L Huston, Jeffrey D Wayne, Heather Neuman, B Mark Smithers, Charlotte E Ariyan, Darius Desai, Jeffrey E Gershenwald, Shlomo Schneebaum, Anja Gesierich, Lisa K Jacobs, James M Lewis, Kelly M McMasters, Cristina O'Donoghue, Andre van der Westhuizen, Armando Sardi, Richard Barth, Robert Barone, J Greg McKinnon, Craig L Slingluff, Jeffrey M Farma, Erwin Schultz, Randall P Scheri, Sergi Vidal-Sicart, Manuel Molina, Alessandro A E Testori, Leland J Foshag, Lisa Van Kreuningen, He-Jing Wang, Myung-Shin Sim, Richard A Scolyer, David E Elashoff, Alistair J Cochran, Mark B Faries
IMPORTANCE: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. OBJECTIVE: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. DESIGN, SETTING, AND PARTICIPANTS: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation...
September 1, 2022: JAMA Surgery
#30
JOURNAL ARTICLE
Li Luo, Ronglai Shen, Arshi Arora, Irene Orlow, Klaus J Busam, Cecilia Lezcano, Tim K Lee, Eva Hernando, Ivan Gorlov, Christopher Amos, Marc S Ernstoff, Venkatraman E Seshan, Anne E Cust, James Wilmott, Richard A Scolyer, Graham Mann, Eduardo Nagore, Pauline Funchain, Jennifer Ko, Peter Ngo, Sharon N Edmiston, Kathleen Conway, Paul B Googe, David Ollila, Jeffrey E Lee, Shenying Fang, Judy R Rees, Cheryl L Thompson, Meg Gerstenblith, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Yvonne Saenger, Adam Z Reynolds, Matthew Schwartz, Tawny Boyce, Sheri Holmen, Elise Brunsgaard, Paul Bogner, Pei Fen Kuan, Charles Wiggins, Nancy E Thomas, Colin B Begg, Marianne Berwick
It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs...
July 25, 2022: Pigment Cell & Melanoma Research
#31
JOURNAL ARTICLE
Anna K Lawless, David J Coker, Serigne N Lo, Tasnia Ahmed, Richard A Scolyer, Sydney Ch'ng, Omgo E Nieweg, Kerwin Shannon, Andrew Spillane, Jonathan R Stretch, John F Thompson, Robyn P M Saw
BACKGROUND: In-transit metastases (ITMs) affect approximately 4% of patients with cutaneous melanoma. This study sought to identify clinical and pathological characteristics that predict further recurrence and survival following resection of ITMs. PATIENTS AND METHODS: Patients (n = 573) who underwent surgical resection of their first presentation of ITM following previous surgical treatment of an American Joint Committee on Cancer (AJCC) stage I-II melanoma between 1969 and 2017 were identified from an institutional database...
October 2022: Annals of Surgical Oncology
#32
Author Correction: Tumour gene expression signature in primary melanoma predicts long-term outcomes.
Manik Garg, Dominique-Laurent Couturier, Jérémie Nsengimana, Nuno A Fonseca, Matthew Wongchenko, Yibing Yan, Martin Lauss, Göran B Jönsson, Julia Newton-Bishop, Christine Parkinson, Mark R Middleton, D Timothy Bishop, Sarah McDonald, Nikki Stefanos, John Tadross, Ismael A Vergara, Serigne Lo, Felicity Newell, James S Wilmott, John F Thompson, Georgina V Long, Richard A Scolyer, Pippa Corrie, David J Adams, Alvis Brazma, Roy Rabbie
No abstract text is available yet for this article.
May 17, 2022: Nature Communications
#33
JOURNAL ARTICLE
Andrew T Li, Jia Miin Yip, Harsham Choksi, Kevin London, Alison J Potter, Serigne N Lo, Robyn P M Saw, Kerwin F Shannon, Ines Pires da Silva, Alexander H R Varey, Alexander M Menzies, Georgina V Long, Brindha Shivalingam, Richard A Scolyer, John F Thompson, Sydney Ch'ng
Primary scalp melanomas are associated with a higher rate of brain metastasis than primary cutaneous melanomas occurring at other head and neck and body sites, but the reason is unclear. Spread to brain parenchyma via emissary veins draining from the scalp to dural sinuses has been suggested. We sought to examine the locations of metastases from primary scalp and nonscalp head and neck melanomas to determine whether there was anatomical evidence supporting direct venous spread to the brain. Data from patients who developed distant metastases from cutaneous head and neck melanomas (CHNMs) between 2000 and 2018 were analyzed...
August 1, 2022: Melanoma Research
#34
JOURNAL ARTICLE
Russell J Diefenbach, Jenny H Lee, Ashleigh Stewart, Alexander M Menzies, Matteo S Carlino, Robyn P M Saw, Jonathan R Stretch, Georgina V Long, Richard A Scolyer, Helen Rizos
Detection of melanoma mutations using circulating tumor DNA (ctDNA) is a potential alternative to using genomic DNA from invasive tissue biopsies. To date, mutations in the GC-rich TERT promoter region, which is commonly mutated in melanoma, have been technically difficult to detect in ctDNA using next-generation sequencing (NGS) panels. In this study, we developed a custom melanoma NGS panel for detection of ctDNA, which encompasses the top 15 gene mutations in melanoma including the TERT promoter. We analyzed 21 stage III and IV melanoma patient samples who were treatment-naïve or on therapy...
2022: Frontiers in Oncology
#35
JOURNAL ARTICLE
Joshua M Weiss, Miranda V Hunter, Nelly M Cruz, Arianna Baggiolini, Mohita Tagore, Yilun Ma, Sandra Misale, Michelangelo Marasco, Theresa Simon-Vermot, Nathaniel R Campbell, Felicity Newell, James S Wilmott, Peter A Johansson, John F Thompson, Georgina V Long, John V Pearson, Graham J Mann, Richard A Scolyer, Nicola Waddell, Emily D Montal, Ting-Hsiang Huang, Philip Jonsson, Mark T A Donoghue, Christopher C Harris, Barry S Taylor, Tianhao Xu, Ronan Chaligné, Pavel V Shliaha, Ronald Hendrickson, Achim A Jungbluth, Cecilia Lezcano, Richard Koche, Lorenz Studer, Charlotte E Ariyan, David B Solit, Jedd D Wolchok, Taha Merghoub, Neal Rosen, Nicholas K Hayward, Richard M White
Oncogenic alterations to DNA are not transforming in all cellular contexts1,2 . This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails3 . We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma...
April 2022: Nature
#36
REVIEW
Anna E B McLean, Steven C Kao, David J Barnes, Keith K H Wong, Richard A Scolyer, Wendy A Cooper, Maija R J Kohonen-Corish
Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile...
January 20, 2022: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
#37
JOURNAL ARTICLE
Pascale Guitera, Andreanne Waddell, Elizabeth Paton, Gerald B Fogarty, Angela Hong, Richard A Scolyer, Jonathan R Stretch, Brett A O'Donnell, Giovanni Pellacani
No abstract text is available yet for this article.
February 2, 2022: Australasian Journal of Dermatology
#38
JOURNAL ARTICLE
Serigne N Lô, Jun Ma, Maurizio Manuguerra, Margarita Moreno-Betancur, Richard A Scolyer, John F Thompson
Competing risks models are attractive tools to analyze time-to-event data where several causes of an event are competing. However, a complexity may arise when, for instance, some subjects experience the event of interest but the causes are not known. Assuming that unknown causes of events are missing at random, we developed a novel constrained maximum penalized likelihood method for fitting semi-parametric cause-specific Cox regression models. Here, penalty functions were used to smooth the baseline hazards...
January 17, 2022: Statistical Methods in Medical Research
#39
JOURNAL ARTICLE
Caitlin R Semsarian, Tara Ma, Brooke Nickel, Richard A Scolyer, Peter M Ferguson, H Peter Soyer, Lisa Parker, Alexandra Barratt, John F Thompson, Katy J L Bell
No abstract text is available yet for this article.
June 2022: British Journal of Dermatology
#40
JOURNAL ARTICLE
Amanda Regio Pereira, Marina Corral-Forteza, Helena Collgros, Mary-Ann El Sharouni, Peter M Ferguson, Richard A Scolyer, Pascale Guitera
BACKGROUND: Around 70% of cutaneous malignant melanomas (MMs) develop de novo, and small-diameter or 'tiny' lesions are expected to represent the earliest manifestation of most MMs. AIM: To describe the clinical, histopathological and dermoscopic features of tiny MMs, and to investigate the impact of imaging tools, including total body photography (TBP) and sequential digital dermoscopy imaging (SDDI) in their detection. METHODS: Consecutive MMs diagnosed over 2 years in a referral centre were retrospectively included...
May 2022: Clinical and Experimental Dermatology
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