Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study.

Background Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4-25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7-31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4-10.3. Limitations The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Malignant melanoma: Underlying epigenetic mechanisms.

Although malignant melanoma is not the most common type of skin cancer, it is the most aggressive and fatal type as it can spread out and metastasize progressively. Early diagnosis and interventions lead to improved patient survival. The incidence rate of melanoma is dramatically increasing, with a few newer therapeutic options available. Therefore, establishing a reliable genetic or epigenetic-based diagnostic and prognostic tool is really important. In this review, we highlight the underlying epigenetic mechanisms involved in melanoma. Furthermore, the epigenetic-based therapeutic options will be also discussed. One of the key areas of discussion will be microRNA which is a small, single-stranded RNA molecule that serves as a regulatory element and found to regulate nearly a third of human genes. MicroRNAs play a role in a wide range of diseases including cancer. In malignant cells, it regulates cell proliferation, invasion, and metastasis.

Identification of novel chemotherapeutic strategies for metastatic uveal melanoma.

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

Genome-wide association study of skin complex diseases.

Complex diseases are caused by both genetic and environmental factors. Over decades, scientists endeavored to uncover the genetic myth of complex diseases by linkage and association studies. Since 2005, the genome-wide association study (GWAS) has been proved to be the most powerful and efficient study design thus far in identifying genetic variants that are associated with complex diseases. More than 230 complex diseases and traits have been investigated by this approach. In dermatology, 10 skin complex diseases have been investigated, a wealth of common susceptibility variants conferring risk for skin complex diseases have been discovered. These findings point to genes and/or loci involved in biological systems worth further investigating by using other methodologies. Certainly, as our understanding of the genetic etiology of skin complex diseases continues to mature, important opportunities will emerge for developing more effective diagnostic and clinical management tools for these diseases.

Screening, early detection, and trends for melanoma: current status (2000-2006) and future directions

In the past 5 years, there have been notable strides toward the earlier recognition and discovery of melanoma, including new technologies to complement and augment the clinical examination and new insights to help clinicians recognize early melanoma. However, incidence and mortality rates throughout most of the developed world have risen over the past 25 years, while education and screening, potentially the best means for reducing the disease, continue to be severely underutilized. Much progress needs to be made to reach middle-aged and older men and persons of lower socioeconomic status who suffer a disproportionate burden of death from melanoma. Worldwide melanoma control must also be a priority, and comprehensive educational and screening programs should be directed to Northern Ireland and a number of Eastern European nations, whose 5-year survival rates range between 53% and 60%, mirroring those of the United States and Australia more than 40 years ago. LEARNING OBJECTIVE: After completing this learning activity, participants should be aware of the most recent melanoma epidemiologic data, both in the United States and internationally; worldwide early detection and screening programs; clinical strategies to recognize and improve the detection of early melanoma; the latest technologies for early detection of melanoma; and public and professional education programs designed to enhance early detection.