Article
Oncology
Anne-Celine Derrien, Manuel Rodrigues, Alexandre Eeckhoutte, Stephane Dayot, Alexandre Houy, Lenha Mobuchon, Sophie Gardrat, Delphine Lequin, Stelly Ballet, Gaelle Pierron, Samar Alsafadi, Odette Mariani, Ahmed El-Marjou, Alexandre Matet, Chrystelle Colas, Nathalie Cassoux, Marc-Henri Stern
Summary: The study identified MBD4 as a new predisposing gene for UM associated with high mutation M3 tumors, leading to increased incidence and high tumor mutation burden in UM. Tumors carrying MBD4 mutations may respond to immunotherapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Review
Biochemistry & Molecular Biology
Pavlina Spiliopoulou, Olga Vornicova, Sofia Genta, Anna Spreafico
Summary: Recent advances in treating cutaneous melanoma have significantly improved patient survival rates by refining disease staging, accurately classifying patient risk, and introducing cancer immunotherapy. Immunotherapy, particularly in the form of immune checkpoint inhibition, has played a crucial role in managing both early and late-stage melanoma and has extended its benefits to other types of skin cancers as well. This review summarizes the current role of immunotherapy in melanoma and non-melanoma skin cancers, highlights important immunotherapy-related molecular biomarkers, and discusses future research directions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Cristina Andres-Zayas, Julia Suarez-Gonzalez, Maria Chicano-Lavilla, Mariana Bastos Oreiro, Gabriela Rodriguez-Macias, Patricia Font Lopez, Santiago Osorio Prendes, Gillen Oarbeascoa Royuela, Patricia Garcia Ramirez, Rocio Nieves Salgado, Ignacio Gomez-Centurion, Diego Carbonell Munoz, Paula Muniz, Mi Kwon, Jose Luis Diez-Martin, Ismael Buno, Carolina Martinez-Laperche
Summary: The study aimed to analyze the genomic characterization of sixteen patients with a strong family or personal onco-hematological history through whole-exome sequencing. Pathogenic or likely pathogenic germline variants were detected in four out of the six families studied, while three P/LP germline variants in genes potentially involved in cancer development were found in the remaining four individuals. Novel candidate genes (NFATC2 and TC2N) potentially related to germline syndromes were identified using next-generation sequencing strategies.
Article
Oncology
Yasmin Soares de Lima, Coral Arnau-Collell, Marcos Diaz-Gay, Laia Bonjoch, Sebastia Franch-Exposito, Jenifer Munoz, Leticia Moreira, Teresa Ocana, Miriam Cuatrecasas, Cristina Herrera-Pariente, Sabela Carballal, Lorena Moreno, Aranzazu Diaz de Bustamante, Antoni Castells, Luis Bujanda, Joaquin Cubiella, Daniel Rodriguez-Alcalde, Francesc Balaguer, Sergi Castellvi-Bel
Summary: Cancer, particularly colorectal cancer, is a major cause of mortality worldwide. Serrated polyposis syndrome (SPS) is a hereditary condition with a higher risk of colorectal cancer, characterized by multiple serrated lesions in the colon. This study identified 14 new genes associated with predisposition to familial SPS, highlighting the importance of genetic factors in assessing and managing colorectal cancer risk in affected families. Further research and replication studies are needed to confirm these findings and improve preventive measures for individuals with SPS.
Article
Oncology
Shaoyu Hao, Ximeng Zhao, Yue Fan, Zhengchuang Liu, Xiang Zhang, Wei Li, Hongling Yuan, Jie Zhang, Yanxiang Zhang, Tonghui Ma, Houquan Tao
Summary: This study found a high prevalence of PGVs in young patients with common late-onset cancers, suggesting their potential clinical implications. Therefore, screening for PGVs is recommended in young patients with lung cancer, liver cancer, colorectal cancer, gastric cancer, renal cancer, or head-neck cancer.
Article
Multidisciplinary Sciences
Charles Q. Yang, Huan Wang, Zhenqiu Liu, Matthew T. Hueman, Aadya Bhaskaran, Donald E. Henson, Li Sheng, Dechang Chen
Summary: This study introduces machine learning as a novel tool to integrate additional prognostic factors into the TNM staging system for more accurate risk classification and survival prediction in patients with cutaneous melanoma. By utilizing the Ensemble Algorithm for Clustering Cancer Data (EACCD), a more advanced prognostic system was developed that improved patient stratification and survival prediction accuracy. The integration of additional factors separated favorable from unfavorable clinical outcomes, enhancing cohort selection for clinical trials and treatment management.
Article
Oncology
Richa Sharma, Ninad Oak, Wenan Chen, Rose Gogal, Martin Kirschner, Fabian Beier, Michael J. Schnieders, Maria Spies, Kim E. Nichols, Marcin Wlodarski
Summary: The study found that germline variants affecting RPA1 are enriched in pediatric cancers, suggesting a potential role of these variants in oncogenesis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Genetics & Heredity
Helen Hanson, Esteban Astiazaran-Symonds, Laura M. Amendola, Judith Balmana, William D. Foulkes, Paul James, Susan Klugman, Joanne Ngeow, Rita Schmutzler, Nicoleta Voian, Myra J. Wick, Tuya Pal, Marc Tischkowitz, Douglas R. Stewart
Summary: Despite the well-known role of CHEK2 germline pathogenic variants in cancer predisposition, there are limited resources for managing CHEK2 heterozygotes in clinical practice. The guidance on clinical management of CHEK2 heterozygotes should be personalized based on risk estimates considering family history and other modifiers. Risk-reducing mastectomy and cancer surveillance should be considered according to personalized risk estimates and shared decision making. Further research is needed to establish the spectrum of CHEK2-associated cancer risks and the outcomes of surveillance, response to treatment, and survival.
GENETICS IN MEDICINE
(2023)
Article
Oncology
C. Loveday, A. Garrett, P. Law, S. Hanks, E. Poyastro-Pearson, J. W. Adlard, J. Barwell, J. Berg, A. F. Brady, C. Brewer, C. Chapman, J. Cook, R. Davidson, A. Donaldson, F. Douglas, L. Greenhalgh, A. Henderson, L. Izatt, A. Kumar, F. Lalloo, Z. Miedzybrodzka, P. J. Morrison, J. Paterson, M. Porteous, M. T. Rogers, L. Walker, D. Eccles, D. G. Evans, K. Snape, H. Hanson, R. S. Houlston, C. Turnbull
Summary: This study is the largest case-control whole-exome analysis of breast cancer to date. While there may be additional breast cancer susceptibility genes, genes of high penetrance are likely to have very low mutational frequency.
ANNALS OF ONCOLOGY
(2022)
Article
Dermatology
Kalle Mattila, Helmi Vihinen, Antti Karlsson, Heikki Minn, Pia Vihinen, Eetu Heervae
Summary: Previous studies have shown that persistent tobacco smoking is associated with lower survival rates in patients with cutaneous melanoma, but the effects of smoking and other prognostic factors have not been extensively studied. This study examined the relationship between smoking (persistent, former, or never) and melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland from 2005 to 2019. The results showed that smoking remained an independent prognostic factor for inferior melanoma-specific survival, regardless of age, sex, stage, and comorbidities. The study also found that smoking was associated with increased melanoma-specific and overall mortality in stage IV patients. Therefore, healthcare professionals should actively inquire about smoking habits in order to support smoking cessation.
ACTA DERMATO-VENEREOLOGICA
(2023)
Review
Oncology
Claire Freycon, Philip J. Lupo, Leora Witkowski, Crystal Budd, William D. Foulkes, Catherine Goudie
Summary: This systematic review found that some patients with FOXO1 fusion-positive ARMS have pathogenic/likely pathogenic variants in cancer predisposing genes, but the causal relationship between CPS and FP-ARMS could not be determined. Only one patient was diagnosed with a cancer predisposition syndrome known to be associated with rhabdomyosarcoma. Clinicians cannot solely rely on FOXO1 fusion status to distinguish patients with/without CPS.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Jilei Ma, Xin Cai, Li Kang, Songfeng Chen, Hongjian Liu
Summary: This study identified 500 differentially expressed genes between cutaneous melanoma samples and normal samples, established a protein-protein interaction network, and found 8 genes significantly correlated to poor survival rate. Additionally, 20 potential small-molecule drugs targeting these genes were discovered, with menadione showing the greatest therapeutic value for melanoma treatment.
Review
Oncology
Jennie Vagher, Amanda Gammon, Wendy Kohlmann, Joanne Jeter
Summary: Although most non-melanoma skin cancers are believed to occur sporadically, there are certain hereditary populations that are predisposed to these tumors. These individuals may be diagnosed with skin cancer at a very young age and/or have multiple primary cancers or tumors in uncommon sites. Understanding the baseline skin cancer risks in these populations is crucial, especially in the context of treatments that may weaken the immune system and further increase the risk of cutaneous malignancies. Additionally, the diagnosis and management of these disorders have significant implications for both patients and their families.
FRONTIERS IN ONCOLOGY
(2022)
Article
Dermatology
Hanna Kuru, Jari Jokelainen, Kaisa Tasanen, Laura Huilaja
Summary: This study retrospectively examined data from 96,304 patients with basal cell carcinoma and 394,503 population controls in Finland, and found that individuals with basal cell carcinoma have an increased risk of other cancers, including lip cancer, mycosis fungoides, and soft tissue cancers.
ACTA DERMATO-VENEREOLOGICA
(2022)
Article
Genetics & Heredity
Ana Mordoh, Juan Carlos Trivino Pardo, Ibel Carri, Maria Marcela Barrio, Jose Mordoh, Mariana Aris
Summary: This study found that genetic events in precursor lesions may contribute to the rapid clinical progression of cutaneous melanoma. The research also revealed a sequential and cumulative pattern of genetic alterations throughout tumorigenesis, suggesting the importance of early genetic changes in tumor development.
BMC MEDICAL GENOMICS
(2023)
Article
Oncology
Elizabeth A. Holland, Serigne Lo, Blake Kelly, Helen Schmid, Anne E. Cust, Jane M. Palmer, Martin Drummond, Nicholas K. Hayward, Antonia L. Pritchard, Graham J. Mann
Summary: A risk prediction model named FRAMe was developed and validated to estimate the likelihood of carrying a heritable CDKN2A mutation in Australian families with increased melanoma risk. Family variables such as age of melanoma diagnosis, number of primary melanomas, and cancer history were independently associated with mutation status. The model had good predictive performance, especially in areas with high melanoma incidence.
Editorial Material
Genetics & Heredity
Vaishnavi Nathan, Jane M. Palmer, Peter A. Johansson, Hayley R. Hamilton, Sunil K. Warrier, William Glasson, Lindsay A. McGrath, Vivian F. S. Kahl, Raja S. Vasireddy, Hilda A. Pickett, Kelly M. Brooks, Antonia L. Pritchard, Nicholas K. Hayward
JOURNAL OF MEDICAL GENETICS
(2021)
Letter
Hematology
Vaishnavi Nathan, Peter A. Johansson, Jane M. Palmer, Hayley R. Hamilton, Madeleine Howlie, Kelly M. Brooks, Nicholas K. Hayward, Antonia L. Pritchard
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Gregory M. Kelly, Fares Al-Ejeh, Robert McCuaig, Francesco Casciello, Nabilah Ahmad Kamal, Blake Ferguson, Antonia L. Pritchard, Sayed Ali, Ines P. Silva, James S. Wilmott, Georgina Long, Richard A. Scolyer, Sudha Rao, Nicholas K. Hayward, Frank Gannon, Jason S. Lee
Summary: The study suggests that LC3B may serve as a biomarker for checkpoint inhibitor blockade to guide patient selection. Additionally, G9a inhibition shows potential in enhancing the efficacy of checkpoint inhibitor blockade and increasing response rates in melanoma patients undergoing immunotherapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Kevin M. Brown, Mai Xu, Michael Sargen, Hyunbum Jang, Mingzhen Zhang, Tongwu Zhang, Bin Zhu, Kristie Jones, Jung Kim, Laura Mendoza, Nicholas K. Hayward, Margaret A. Tucker, Alisa M. Goldstein, Xiaohong Rose Yang, Douglas R. Stewart, Belynda Hicks, Dario Consonni, Angela C. Pesatori, Maria Concetta Fargnoli, Ketty Peris, Alex Stratigos, Chiara Menin, Paola Ghiorzo, Susana Puig, Eduardo Nagore, Thorkell Andresson, Ruth Nussinov, Donato Calista, Maria Teresa Landi
Summary: A novel NRAS variant was identified in an Italian melanoma-prone family, absent in other populations, influencing signaling pathways differently than other RAS activating alterations. Further investigation into NRAS as a familial melanoma gene is warranted.
Article
Dermatology
Susan J. Robertson, Lisa Orme, Rodrigo Teixeira, Maryam Shamassi, Felicity Newell, Ann-Marie Patch, Iwei Yeh, Grace Gard, James Wilmott, Louise Jackett, Philip LeBoit, Andrew Fellowes, Grant MacArthur, Stephen Fox, Nicholas K. Hayward, Boris Bastian, Richard Scolyer, Nicola Waddell, Anthony Penington, Mark Shackleton
Summary: Spitz nevi, benign melanocytic neoplasms classically occurring in childhood, have been associated with oncogenic gene fusions in rare agminated cases. A case study found a strong response to treatment with the tyrosine kinase inhibitor, crizotinib, in agminated Spitz nevi with GOPC-ROS1 fusions, demonstrating a new treatment option for lesions where surgery is contraindicated.
Review
Oncology
Michele Carbone, Harvey Pass, Guntulu Ak, H. Richard Alexander, Paul Baas, Francine Baumann, Andrew M. Blakely, Raphael Bueno, Aleksandra Bzura, Giuseppe Cardillo, Jane E. Churpek, Irma Dianzani, Assunta De Rienzo, Mitsuru Emi, Salih Emri, Emanuela Felley-Bosco, Dean A. Fennell, Raja M. Flores, Federica Grosso, Nicholas K. Hayward, Mary Hesdorffer, Chuong D. Hoang, Peter A. Johansson, Hedy L. Kindler, Muaiad Kittaneh, Thomas Krausz, Aaron Mansfield, Muzaffer Metintas, Michael Minaai, Luciano Mutti, Maartje Nielsen, Kenneth O'Byrne, Isabelle Opitz, Sandra Pastorino, Francesca Pentimalli, Marc de Perrot, Antonia Pritchard, Robert Taylor Ripley, Bruce Robinson, Valerie Rusch, Emanuela Taioli, Yasutaka Takinishi, Mika Tanji, Anne S. Tsao, A. Murat Tuncer, Sebastian Walpole, Andrea Wolf, Haining Yang, Yoshie Yoshikawa, Alicia Zolondick, David S. Schrump, Raffit Hassan
Summary: The most common malignancies that develop in carriers of BAP1 germline mutations include mesothelioma, melanoma, renal cell carcinoma, and other tumor types. The features of malignancies can vary among individuals, and a multidisciplinary approach is required for diagnosis and treatment. Detecting BAP1 germline mutations has significant medical, social, and economic impact.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Review
Oncology
Chloe B. Rodgers, Colette J. Mustard, Ryan T. McLean, Sharon Hutchison, Antonia L. Pritchard
Summary: B-cell system plays an important role in the immune response to melanoma. However, there are still disagreements in various aspects of this role. Tumor-infiltrating B-cells have contradictory prognostic values, potentially due to disagreements in cell subset classification and marker usage. Tertiary lymphoid structures (TLS) in tumors, which organize T-cells and B-cells, are associated with improved survival when treated with immune checkpoint blockade. Autoantibody production is increased in melanoma patients, but consistent targets have not been identified yet. The function of antibodies is determined by their isotype and subclass, with IgG(4) being immunosuppressive and correlated with poor patient survival in melanoma.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Review
Oncology
Natasa Broit, Peter A. Johansson, Chloe B. Rodgers, Sebastian T. Walpole, Nicholas K. Hayward, Antonia L. Pritchard
Summary: The study conducted a comprehensive systematic meta-analysis of genomic aberrations in acral melanoma (AM). It identified significantly mutated genes and frequent copy-number aberrations, highlighting potential therapeutic targets.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Oncology
Felicity Newell, Peter A. Johansson, James S. Wilmott, Katia Nones, Vanessa Lakis, Antonia L. Pritchard, Serigne N. Lo, Robert 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 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 Pearson, Richard A. Scolyer, Nicola Waddell, Nicholas K. Hayward
Summary: This is the largest whole-genome analysis of melanoma to date, comprehensively comparing the genomics of the four major melanoma subtypes. This study highlights both similarities and differences between the subtypes, providing insights into the etiology and biology of melanoma.
Article
Oncology
Peter A. Johansson, Nicholas K. Hayward, Antonia L. Pritchard
Summary: Immune checkpoint inhibitors (ICIs) have improved survival in advanced cutaneous melanoma. Gene expression associated with response to ICI has been investigated and found to be predictive of survival not only in ICI-treated patients but also in those who never received ICI.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Oncology
Hansol Lee, Angela L. Ferguson, Camelia Quek, Ismael A. Vergara, Ines Pires daSilva, Ruth Allen, Tuba Nur Gide, Jordan W. Conway, Lambros T. Koufariotis, Nicholas K. Hayward, Nicola Waddell, Matteo S. Carlino, Alexander M. Menzies, Robyn P. M. Saw, Elena Shklovskaya, Helen Rizos, Serigne Lo, Richard A. Scolyer, Georgina V. Long, Umaimaintha Palendira, James S. Wilmott
Summary: This study characterized intratumoral macrophage populations in melanoma biopsies and investigated the association between CD16-expressing macrophage densities and treatment outcomes for patients receiving anti-PD-1 monotherapy or a combination with anti-CTLA-4. The results showed that patients who responded to combination therapy had higher CD16 macrophage densities compared to those who did not respond. Additionally, patients with high intratumoral densities of CD16 macrophages had a significantly longer progression-free survival. These findings suggest that CD16 macrophages may serve as a potential biomarker for response to combination immunotherapies in metastatic melanoma patients.
CLINICAL CANCER RESEARCH
(2023)
Letter
Dermatology
Peter A. Johansson, Jane M. Palmer, Hayley R. Hamilton, David C. Whiteman, Antonia L. Pritchard, Nicholas K. Hayward
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)