PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux
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Background: Acral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear. Objective: To investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma. Methods: A retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors. Results: The heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were observed in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p= 0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p＞0.05). Conclusion: PTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients.
Abstract
Background: Acral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear. Objective: To investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma. Methods: A retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors. Results: The heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were observed in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p= 0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p＞0.05). Conclusion: PTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients.
참고문헌 (33)
- Viros A, "Improving melanoma classification by integrating genetic and morphologic features", PLoS Med, 5, pp.e120~ (2008)
- Hayward NK, "Whole-genome landscapes of major melanoma subtypes", Nature, 545, pp.175~180 (2017)
- Merkel EA, "Malignant melanoma of sun-protected sites: a review of clinical, histological, and molecular features", Lab Invest, 97, pp.630~635 (2017)
- 장홍선, "Comparison of Melanoma Subtypes among Korean Patients by Morphologic Features and Ultraviolet Exposure", Annals of Dermatology, 26(4), pp.485~490 (2014), 대한피부과학회
- Wang Y, "Racial differences in six major subtypes of melanoma : descriptive epidemiology", BMC Cancer, 16, pp.691~ (2016)
- Alexandrov LB, "Signatures of mutational processes in human cancer", Nature, 500, pp.415~421 (2013)
- Zebary A, "KIT, NRAS, BRAF and PTEN mutations in a sample of Swedish patients with acral lentiginous melanoma", J Dermatol Sci, 72, pp.284~289 (2013)
- Liau JY, "TERT promoter mutation is uncommon in acral lentiginous melanoma", J Cutan Pathol, 41, pp.504~508 (2014)
- Carrera C, "Clinical, epidemiological, and molecular heterogeneity in acral melanoma", J Invest Dermatol, 138, pp.254~255 (2018)
- de Unamuno Bustos B, "Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma", Br J Dermatol, 179, pp.394~404 (2018)
- Roh MR, "Promoter methylation of PTEN is a significant prognostic factor in melanoma survival", J Invest Dermatol, 136, pp.1002~1011 (2016)
- Minagawa A, "Melanomas and mechanical stress points on the plantar surface of the foot", N Engl J Med, 374, pp.2404~2406 (2016)
- Costello CM, "Acral melanoma and mechanical stress on the plantar surface of the foot", N Engl J Med, 377, pp.395~396 (2017)
- Rambhia PH, "Predominance of oral mucosal melanoma in areas of high mechanical stress", J Am Acad Dermatol, 80, pp.1133~1135 (2019)
- Hosokawa M, "Plantar malignant melanoma. Statistical and clinicopathological studies", J Dermatol, 7, pp.137~142 (1980)
- Dwyer PK, "Plantar malignant melanoma in a white Caucasian population", Br J Dermatol, 128, pp.115~120 (1993)
- Jung HJ, "A clinicopathologic analysis of 177 acral melanomas in Koreans : relevance of spreading pattern and physical stress", JAMA Dermatol, 149, pp.1281~1288 (2013)
- Stucke S, "Spatial relationships between shearing stresses and pressure on the plantar skin surface during gait", J Biomech, 45, pp.619~622 (2012)
- Galica AM, "Hallux valgus and plantar pressure loading : the Framingham foot study", J Foot Ankle Res, 6, pp.42~ (2013)
- Skopljak A, "Pedobarography in diagnosis and clinical application", Acta Inform Med, 22, pp.374~378 (2014)
- 이의형, "Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions", Cancer Research and Treatment, 50(4), pp.1378~1387 (2018), 대한암학회
- Roh MR, "Telomerase reverse transcriptase(TERT)promoter mutations in Korean melanoma patients", Am J Cancer Res, 7, pp.134~138 (2017)
- Vazquez Vde L, "Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas", Melanoma Res, 26, pp.93~99 (2016)
- Boer J, "The role of mechanical stress in hidradenitis suppurativa", Dermatol Clin, 34, pp.37~43 (2016)
- Sheen YS, "A clinicopathological analysis of 153 acral melanomas and the relevance of mechanical stress", Sci Rep, 7, pp.5564~ (2017)
- "Pressure ulcers in America: prevalence, incidence, and implications for the future. An executive summary of the National Pressure Ulcer Advisory Panel monograph", Adv Skin Wound Care, 14, pp.208~215 (2001)
- Hodges GJ, "The role of shear stress on cutaneous microvascular endothelial function in humans", Eur J Appl Physiol, 117, pp.2457~2468 (2017)
- Liu S, "Fluid shear stress induces epithelial-mesenchymal transition(EMT)in Hep-2 cells", Oncotarget, 7, pp.32876~32892 (2016)
- Mikhail M, "PTEN expression in melanoma: relationship with patient survival, Bcl-2 expression, and proliferation", Clin Cancer Res, 11, pp.5153~5157 (2005)
- Zhou XP, "Epigenetic PTEN silencing in malignant melanomas without PTEN mutation", Am J Pathol, 157, pp.1123~1128 (2000)
- Bucheit AD, "Complete loss of PTEN protein expression correlates with shorter time to brain metastasis and survival in stage IIIB", C melanoma patients with BRAFV600 mutations, 2014, pp.20, 5527~5536
- Giles KM, "Revisiting the clinical and biologic relevance of partial PTEN loss in melanoma", J Invest Dermatol, 139, pp.430~438 (2019)
- Hopkins BD, "Molecular pathways : intercellular PTEN and the potential of PTEN restoration therapy", Clin Cancer Res, 20, pp.5379~5383 (2014)