JAAD International (Jun 2023)
Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case seriesCapsule Summary
- Alisa M. Goldstein, PhD,
- Richard Qin, BS,
- Emily Y. Chu, MD, PhD,
- David E. Elder, MBChB,
- Daniela Massi, MD, PhD,
- David J. Adams, PhD,
- Paul W. Harms, MD, PhD,
- Carla Daniela Robles-Espinoza, PhD,
- Julia A. Newton-Bishop, MD, PhD,
- D. Timothy Bishop, PhD,
- Mark Harland, PhD,
- Elizabeth A. Holland, BSc,
- Anne E. Cust, PhD,
- Helen Schmid, MPH,
- Graham J. Mann, MBBS, PhD,
- Susana Puig, MD, PhD,
- Miriam Potrony, PhD,
- Llucia Alos, MD, PhD,
- Eduardo Nagore, MD, PhD,
- David Millán-Esteban, PhD,
- Nicholas K. Hayward, PhD,
- Natasa Broit, PhD,
- Jane M. Palmer, RN,
- Vaishnavi Nathan, PhD,
- Elizabeth G. Berry, MD,
- Esteban Astiazaran-Symonds, MD,
- Xiaohong R. Yang, PhD,
- Margaret A. Tucker, MD,
- Maria Teresa Landi, MD, PhD,
- Ruth M. Pfeiffer, PhD,
- Michael R. Sargen, MD
Affiliations
- Alisa M. Goldstein, PhD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Richard Qin, BS
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Emily Y. Chu, MD, PhD
- Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- David E. Elder, MBChB
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- Daniela Massi, MD, PhD
- Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy
- David J. Adams, PhD
- Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, England
- Paul W. Harms, MD, PhD
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
- Carla Daniela Robles-Espinoza, PhD
- Experimental Cancer Genetics, The Wellcome Trust Sanger Institute, Hinxton, England; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Santiago de Querétaro, Qro, Mexico
- Julia A. Newton-Bishop, MD, PhD
- Division of Haematology and Immunology, Institute of Medical Research at St James’s, University of Leeds, Leeds, England
- D. Timothy Bishop, PhD
- Division of Haematology and Immunology, Institute of Medical Research at St James’s, University of Leeds, Leeds, England
- Mark Harland, PhD
- Division of Haematology and Immunology, Institute of Medical Research at St James’s, University of Leeds, Leeds, England
- Elizabeth A. Holland, BSc
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council, NSW, Sydney, Australia; Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia
- Anne E. Cust, PhD
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council, NSW, Sydney, Australia; Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Helen Schmid, MPH
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council, NSW, Sydney, Australia; Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Graham J. Mann, MBBS, PhD
- Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
- Susana Puig, MD, PhD
- Melanoma Unit, Department of Dermatology, Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain; Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
- Miriam Potrony, PhD
- Centre of Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain; Melanoma Unit, Biochemistry and Molecular Genetics Department, Hospital Clínic de Barcelona, IDIBAPS, Barcelona University, Barcelona, Spain
- Llucia Alos, MD, PhD
- Pathology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
- Eduardo Nagore, MD, PhD
- Department of Dermatology, Fundación Instituto Valenciano de Oncología, València, Spain; School of Medicine, Universidad Católica de València San Vicente Mártir, València, Spain
- David Millán-Esteban, PhD
- Department of Dermatology, Fundación Instituto Valenciano de Oncología, València, Spain; School of Medicine, Universidad Católica de València San Vicente Mártir, València, Spain
- Nicholas K. Hayward, PhD
- QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
- Natasa Broit, PhD
- QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
- Jane M. Palmer, RN
- QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
- Vaishnavi Nathan, PhD
- QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
- Elizabeth G. Berry, MD
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon
- Esteban Astiazaran-Symonds, MD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Xiaohong R. Yang, PhD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Margaret A. Tucker, MD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Maria Teresa Landi, MD, PhD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Ruth M. Pfeiffer, PhD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
- Michael R. Sargen, MD
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; Correspondence and reprint requests to: Michael R. Sargen, MD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr, Room 6E-542, Rockville, MD 20850.
- Journal volume & issue
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Vol. 11
pp. 43 – 51
Abstract
Background: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation. Objective: To assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT) commonly exhibit spitzoid morphology. Methods: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist. Results: Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in POT1, TERF2IP, ACD, and TERT, respectively. Compared to noncarriers (n = 139 melanomas), POT1 carriers (OR = 225.1, 95% confidence interval: 51.7-980.5; P < .001) and individuals with TERF2IP, ACD, and TERT variants (OR = 82.4, 95% confidence interval: 21.3-494.6; P < .001) had increased odds of spitzoid morphology. Limitations: Findings may not be generalizable to nonfamilial melanoma cases. Conclusion: Spitzoid morphology in familial melanoma could suggest germline alteration of TMG.
