Genomic progression for local invasion of cutaneous squamous cell carcinoma from the superficial to the deep portion.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. While many treatments exist, our understanding of its genomic progression, especially from the epidermis to the deep dermis, remains limited. This study aims to identify genetic mutations associated with the progression of cSCC into the deep dermis, providing insights into its aggressive behavior and high-risk features. We performed high-depth whole-exome sequencing on 12 cSCC tissues, along with paired normal tissues from six patients, using microdissection techniques. The mutational analysis focused on identifying alterations enriched during cSCC progression. Gene Ontology enrichment analysis, immunohistochemical assays, and external single-cell RNA data were utilized for validation. A total of 8863 non-synonymous somatic mutations were identified in 4092 genes across the superficial and deep portions of cSCCs. Analysis of deep portion mutations revealed a significant correlation with gene ontology biological processes, particularly cell junction organization, and cell-cell adhesion. Clonal mutations in these processes were more prevalent in the deep portions, indicating their impact on the cSCC mutation landscape. Genetic evolution analysis identified 29 causal genes associated with dermal invasion in cSCC. We highlight somatic mutations in cSCC, revealing heterogeneity between superficial and deep regions. Altered genes in cell junction organization and cell-cell adhesion emerged as pivotal in dermal invasion. We identified 29 causal genes primarily in deep tumor regions. Our findings emphasize analyzing multiple tumor regions to capture varied mutational landscapes. These insights advance our understanding of cSCC progression, emphasizing genetic and cellular changes during tumor evolution.

Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

Comparison of risk allele frequencies of single nucleotide polymorphisms associated with age-related macular degeneration in different ethnic groups.

BACKGROUND: The prevalence of age-related macular degeneration (AMD) varies from 6.8 to 18.3% for all forms of AMD and from 0.6 to 2.6% for late AMD according to race, suggesting the existence of genetic differences among races. The purpose of this study was to determine the genetic causes of differences in the prevalence of AMD among individuals of different races. METHODS: We collected 138 AMD-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact tests to assess whether the effect allele at a given SNP was significantly enriched or depleted in the database. RESULTS: European, American, and South Asian populations showed similar heatmap patterns, whereas East Asian, and Korean populations had distinct patterns. Korean populations exhibited patterns that were different from those of the other groups; rs5754227 (SYN3), rs1626340 (TGFBR1/COL15A1), rs3750846(ARMS2/HTRA1), and rs9564692 (B3GALTL) were enriched, whereas rs2230199 (C3) and rs73036519 (EXOC3L2/MARK4) were depleted in Koreans; these SNPs are associated with late AMD. The genetic risk score calculated from allele frequencies was not less in East Asians than in Europeans. CONCLUSION: The prevalence of AMD is lower in Asians than in Europeans. However, our study showed that genetic risk scores in East Asians were similar to those in Europeans, which may explain why the global projected number of people with AMD by 2040 is in largest for East Asians, including Koreans.

The concept of nail matrix onychodermis (onychomatricodermis) in the nail unit: Histology and elastin immunohistochemistry.

BACKGROUNDS: We previously demonstrated the presence of onychodermis below nail matrix and nail bed. Because nail matrix is a producer of nail plate, we hypothesized that onychodermis below nail matrix could be the nail counterpart of follicular dermal papilla. In this study, we sought to further characterize histologic, histochemical, and immunohistochemical features of nail matrix onychodermis. METHODS AND RESULTS: Hematoxylin and eosin slides of 10 polydactyly nail units and 10 nail matrix biopsies from children and adults were reviewed. In polydactyly nail units, the onychodermis beneath nail matrix was characterized by onychofibroblasts showing abundant cytoplasm, and this area was slightly separated from the undersurface of the nail matrix. Nail matrix biopsy specimens also showed similar histology in the nail matrix onychodermis. Alcian blue stain demonstrated mucin deposition in onychofibroblasts within the nail matrix onychodermis. Immunohistochemically, elastin was rarely expressed in the nail matrix onychodermis while it was strongly expressed in the dermis of other areas of polydactyly nail units. Elastin was not expressed in follicular dermal papilla of terminal hair follicles of the scalp. CONCLUSION: Our findings demonstrate the presence and localization of nail matrix onychodermis (onychomatricodermis). Our study also demonstrates similar elastin expression patterns in the onychomatricodermis and follicular dermal papilla.

Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer.

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer.

The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N = 4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH). Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5' fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular target therapy.

Mutational profiling of acral melanomas in Korean populations.

The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasian populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profiling of AM and matched normal tissues in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs from patients' saliva DNA were analysed by next-generation sequencing. Only mutations confirmed via digital droplet PCR or in BRAF, KIT and NRAS, the most frequently altered cancer genes in cutaneous melanoma, were considered as positive. The relationship between mutational status and clinicopathological features were examined. Of the 47 AM patients screened, alteration of BRAF, NRAS and KIT genes was observed in 6.4%, 4.3% and 8.5%, respectively. We also tested matched normal tissues of patients to identify tumor-specific mutations. Examination of the mutational profile in a cohort of 28 primary melanomas and matched normal controls found BRAF mutations in two cases (7.1%), KIT mutations in three cases (10.7%) and CTNNB1 mutations in one case (3.6%). The BRAF, NRAS and KIT mutation status did not correlate with clinicopathological characteristics. Our results show that KIT, NRAS and BRAF hotspot mutations occur at a low frequency in Korean populations. We also observed a case with the CTNNB1 mutation, which raises the possibility that other pathways are associated with AM development.

Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area.

Subungual melanoma is a rare subtype of melanoma that usually originates and spreads from the nail matrix. Because of its poor prognosis and short matrix-to-bone distance, amputation has been traditionally performed. Recently, conservative surgery has been attempted for early subungual melanoma, but the evidence supporting this practice is sparse. As little is known about the progression pattern of subungual melanoma, further advances on the subject may provide better guidance on the optimal surgical approach. Histopathology slides, clinical records, and photographs of 23 cases of subungual melanoma were reviewed. For all cases, each area of the nail unit-proximal nail fold, nail matrix, nail bed, and/or hyponychium-in longitudinal sections was available for histological examination. Growth pattern, dermal invasion, and thickness were assessed in each area of the nail unit. There were five cases of melanoma in situ. Eighteen cases showed dermal invasion in at least one area of the nail unit. There were no cases showing dermal invasion in the nail matrix area only. In four cases, dermal invasion involved areas of the nail unit other than the nail matrix. In 14 cases, dermal invasion involved the nail matrix area as well as other areas of the nail unit. Except for one case, the nail matrix area showed thinner dermal invasion compared with dermal invasion in other areas of the nail unit. In conclusion, dermal invasion of subungual melanoma in the nail matrix area tends to occur later than other areas of the nail unit. Longitudinal incisional biopsy is necessary to accurately evaluate melanoma invasion. The findings of this study suggest that conservative surgical treatment for early subungual melanoma may be justified as the nail matrix area, an area of thin dermis and close proximity to the underlying bone, appears to be more resistant to invasion.

The Quality of Life and Psychosocial Impact on Female Pattern Hair Loss.

BACKGROUND: Alopecia, a benign dermatologic condition affecting both genders, particularly harms female patients due to psychosocial effects. Female pattern hair loss (FPHL), the primary cause of hair loss in women, lacks sufficient Korean epidemiological studies examining its psychosocial aspects. OBJECTIVE: This study aimed to explore FPHL's psychosocial impacts, including quality of life (QoL), depression, anxiety, medical consumption, and hair loss factors in Korean women. METHODS: A total of 202 patients with FPHL were interviewed using a validated questionnaire to assess the QoL, psychological impact, and pattern of medical consumption. The severity of hair loss was evaluated using the "basic and specific (BASP) classification" by dermatologists. The Hair-Specific Skindex-29 (HSS29) was used to assess the QoL and Beck depression inventory (BDI), Beck anxiety inventory (BAI) to evaluate psychological aspects, and medical expenses and the number of clinic visits to determine medical consumption. RESULTS: The global HSS29 score of FPHL was 40.97±18.92, indicating a notable impact on QoL. The mean BDI and BAI scores were 14.47 and 10.06, respectively. In multivariable regression analysis, HSS29, BDI, and BAI scores were most affected by the severity of hair loss (p<0.001). CONCLUSION: FPHL damages the psychosocial aspects of patients, such as QoL, depression, and medical consumption, according to the severity of hair loss.

Comparison of Risk Allele Frequencies of Psoriasis-Associated Single-Nucleotide Polymorphisms in Different Population Groups.

BACKGROUND: The prevalence of psoriasis differs by population, and it appears to be more common among Europeans than in East Asians. Recent genome-wide association studies (GWAS) have identified alleles that increase the risk of psoriasis, and these alleles may present different frequencies in different geographic regions. OBJECTIVE: We aimed to gain insights into the causes of differences in disease frequencies according to populations and the factors affecting prevalence and pattern differences. METHODS: We collected a total of 147 psoriasis-associated single-nucleotide polymorphisms (SNPs) from the GWAS catalog and compared the allele frequency differences in 27 populations using public population frequency in the 1000 Genomes Project phase 3 (n=2,504) and the Korean Reference Genome Database (n=1,722). Additionally, we calculated the composited genetic risk scores across the population groups. RESULTS: There were distinct patterns of allele frequencies in different population groups. In many cases, East Asians exhibited allele frequencies opposite to that of Europeans. The genetic risk score was higher in Europeans (average: 0.487) and Americans (average: 0.492) than in East Asians (average: 0.471). The prevalence of psoriasis correlated with the average genetic risk score of the population. CONCLUSION: We observed a difference in the allele frequencies of psoriasis-associated SNPs between the studied populations. This result suggests that the difference in the prevalence of psoriasis between population groups can be interpreted to some extent by the genotype.

Guidelines for the Management of Patients with Alopecia Areata in Korea: Part I Topical and Device-based Treatment.

BACKGROUND: Alopecia areata (AA) is a chronic disease with an unpredictable disease course and severe psychological impact. OBJECTIVE: To provide evidence- and consensus-based insights regarding the treatment of patients with AA in Korea. METHODS: We searched for relevant studies on the topical and device-based treatment of AA in the literature from inception until May 2021. Evidence-based recommendations were also prepared. The evidence for each statement was graded and classified according to the strength of the recommendations. Hair experts from the Korean Hair Research Society (KHRS) voted on the statements, and an agreement of 75% or greater was considered as consensus. RESULTS: Currently, there remains a scarcity of topical treatments, which is supported by robust evidence from a number of high-quality randomized controlled trials. Current evidence supports the efficacy of topical corticosteroids, corticosteroid intralesional injection, and contact immunotherapy in AA patients. Topical corticosteroids and contact immunotherapy are recommended for pediatric AA. A consensus was achieved in 6 out of 14 (42.8%), and 1 out of 5 (20.0%) statements pertaining to topical and device-based treatments in AA, respectively. The expert consensus was from a single country, and the study may not cover all the treatments used. CONCLUSION: The present study provides up-to-date, evidence-based treatment guidelines for AA based on the consensus reached among experts after considering regional healthcare circumstances, adding diversity to the previous guidelines.

Guidelines for the Management of Patients with Alopecia Areata in Korea: Part II Systemic Treatment.

BACKGROUND: Alopecia areata (AA) is a chronic disease with an unpredictable course and can have a severe psychological impact on an individual. OBJECTIVE: To provide evidence and consensus-based statements regarding the treatment of patients with AA in Korea. METHODS: We searched for relevant studies from inception to May 2021 regarding the systemic treatment of AA. Evidence-based recommendations were also prepared. The evidence for each statement was graded and classified according to the strength of the recommendations. Hair experts from the Korean Hair Research Society (KHRS) voted on the statement, and an agreement of 75% or greater was considered as having reached consensus. RESULTS: Current evidence supports the efficacy of systemic corticosteroids, oral cyclosporine monotherapy or combination with systemic corticosteroids, and oral Janus kinase inhibitors in severe AA patients. Systemic steroids may be considered for pediatric patients with severe AA. A consensus was achieved in three out of nine (33.3%), and one out of three (33.3%) statements pertaining to systemic treatment in adult and pediatric AA, respectively. CONCLUSION: The present study produced up-to-date, evidence-based treatment guidelines for AA associated with the consensus obtained by experts based on the Korean healthcare system.

The presence and localization of onychodermis (specialized nail mesenchyme) containing onychofibroblasts in the nail unit: a morphological and immunohistochemical study.

AIMS: Due to its limited availability there has been very little research on the mesenchyme of the nail unit. Recently, we discovered specialized mesenchymal cells beneath the nail matrix and proposed to call them onychofibroblasts. The purpose of this study was to further delineate more precisely by histology and immunohistochemistry the specialized nail mesenchyme. METHODS AND RESULTS: Thirty supernumerary digits were obtained during operations to correct polydactyly. Longitudinal and transverse sections were obtained from formalin-fixed paraffin-embedded blocks. In sections stained with haematoxylin and eosin, a mesenchymal area that showed much more cellularity and less eosinophilic, loose connective tissue was identified beneath the nail matrix and nail bed. Using Alcian blue staining, mucin was detected in this mesenchymal area below the nail matrix and nail bed. Immnunohistochemically, CD10 and versican were expressed strongly in the mesenchyme containing onychofibroblasts under the nail matrix and nail bed. CONCLUSIONS: These results demonstrate the presence and localization of a specialized nail mesenchyme containing onychofibroblasts in a well-defined area beneath the nail matrix and nail bed. Thus, we propose the term onychodermis for this specialized nail mesenchyme that is histologically and immunohistochemically distinct from the dermis of other parts of the nail unit.

World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphoma in Korea: a retrospective study at a single tertiary institution.

BACKGROUND: The relative frequency and the clinicopathological characteristics of lymphoma may vary according to geography and ethnicity. Data are limited regarding the features of cutaneous lymphoma (CL) presented according to the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) classification (2005) in Korea. OBJECTIVE: The study determined the relative frequency of CL in Korea and presented the clinical relevance of CL based on the WHO-EORTC classification. METHODS: We reclassified the cases of CL collected over a 16-year period in a tertiary institution-based dermatologic setting in Korea. RESULTS: In all, 164 cases were divided into 96 primary and 68 secondary CL. The group of primary CL consisted of T- and natural killer-cell lymphomas (84.3%), B-cell lymphomas (13.5%), and immature hematopoietic malignancies (2%). The Korean population presented with a higher rate of T-cell and natural killer-/T-cell CL and a lower rate of cutaneous B-cell lymphoma than Western countries. Compared with 2003 Korean data, the rate of mycosis fungoides was lower and the rate of nasal and nasal-type natural killer-/T-cell lymphomas was higher. LIMITATIONS: This study was retrospective and based on a single-center experience. CONCLUSION: As the relative frequency of lymphomas differs widely with geography and ethnicity, there is a need to collect more data to describe the epidemiologic characteristics in the Far East.

Risk Allele Frequency Analysis and Risk Prediction of Single-Nucleotide Polymorphisms for Prostate Cancer.

The incidence of prostate cancer (PCa) varies by ethnicity. This study aimed to provide insights into the genetic cause of PCa, which can result in differences in incidence among individuals of diverse ancestry. We collected data on PCa-associated single-nucleotide polymorphisms (SNPs) from a genome-wide association study catalog. Fisher's exact tests were used to analyze the significance of enrichment or depletion of the effect on the allele at a given SNP. A network analysis was performed based on PCa-related SNPs that showed significant differences among ethnicities. The SNP-based polygenic risk score (PRS) was calculated, and its correlation with PCa incidence was evaluated. European, African, and East Asian populations had different heatmap patterns. Calculated PRS from the allele frequencies of PCa was the highest among Africans, followed by Europeans, and was the lowest among East Asians. PRS was positively correlated with the incidence and mortality of PCa. Network analysis revealed that AR, CDKN1B, and MAD1L1 are genes related to ethnic differences in PCa. The incidence and mortality of PCa showed a strong correlation with PRS according to ethnicity, which may suggest the effect of genetic factors, such as the AR gene, on PCa pathogenesis.

Clinical efficacy of adipocyte-derived stem cells conditioned media combined with micro-injury in refractory patch of alopecia areata.

Management of alopecia areata (AA) is often challenging especially when patients have AA lesion refractory to conventional treatments such as corticosteroids, contact immunotherapy, and systemic therapy. Reports indicate adipocyte-derived stem cell conditioned media (ASC-CM) can activate hair growth and micro-injury using fractional laser or microneedling can also induce wound healing and hair regeneration, which suggests ASC-CM combined with fractional laser or microneedling might provide alternative therapeutic option for a refractory patch of AA. This study aimed to evaluate the clinical efficacy and safety of ASC-CM combined with 10,600 nm carbon dioxide fractional laser or microneedling for the treatment of refractory patch of AA. This retrospective study was based on evaluations of 14 patients with a refractory patch of AA treated with ASC-CM, combined with a 10,600 nm carbon dioxide fractional laser, or microneedling from March 2017 to August 2020. The efficacy of treatment was assessed by extents of hair regrowth percentages of involved areas. Of the 14 enrolled patients, 9 (64.3%) showed > 50% hair regrowth and 6 patients (42.9%) showed complete recovery. In the responder group (n = 9), mean period to achieve > 50% hair regrowth was 11.3 weeks (range 8-16 weeks). In the non-responder group (n = 5), 4 patients (28.6%) showed < 25% of hair regrowth and 1 patient show slight hair regrowth (7.1%) after 3 months of treatment. This study showed ASC-CM combined with 10,600 nm carbon dioxide fractional laser or microneedling may offer effective and safe treatment options for a refractory patch of AA.

Risk Allele Frequency Analysis of Single-Nucleotide Polymorphisms for Vitamin D Concentrations in Different Ethnic Group.

The prevalence of vitamin D deficiency varies from 20.8% to 61.6% among populations of different ethnicities, suggesting the existence of a genetic component. The purpose of this study was to provide insights into the genetic causes of vitamin D concentration differences among individuals of diverse ancestry. We collected 320 single-nucleotide polymorphisms (SNPs) associated with vitamin D concentrations from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact tests to assess the significance of the enrichment or depletion of the effect allele at a given SNP in the database. In addition, we calculated the SNP-based genetic risk score (GRS) and performed correlation analysis with vitamin D concentration that included latitude. European, American, and South Asian populations showed similar heatmap patterns, whereas African, East Asian, and Korean populations had distinct ones. The GRS calculated from allele frequencies of vitamin D concentration was highest among Europeans, followed by East Asians and Africans. In addition, the difference in vitamin D concentration was highly correlated with genetic factors rather than latitude effects.

Analysis of risk allele frequencies of single nucleotide polymorphisms related to open-angle glaucoma in different ethnic groups.

BACKGROUND: The prevalence of open-angle glaucoma (OAG) varies from 0.5% to 7.0% among populations of diverse ancestry, suggesting the existence of genetic differences. The purposes of this study were to provide insights into genetic causes of OAG, which can result in prevalence and phenotype differences among populations of diverse ancestry for OAG, and to compare allele frequencies of intraocular pressure (IOP) elevation-related SNPs in OAG among Koreans and other ethnic groups. METHODS: We collected the data on a total of 135 OAG-associated single nucleotide polymorphisms (SNPs) from a genome-wide association studies (GWAS) catalog. The population-level allele frequencies of these SNPs were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact test to assess whether the effect allele at a given SNP was significantly enriched or depleted. RESULTS: European, American, and South Asian populations showed similar heatmap patterns, while African, East Asian, and Korean populations had distinct patterns. Korean population presented different profiles compared to other groups; rs1579050 (FMNL2 gene), rs2024211 (CAV2;CAV1), and rs8141433 (GNB1L;TXNRD2 gene), which are known to be associated with IOP variation, were enriched in Americans, Europeans, and Africans, and depleted in Koreans. These can be the candidates for the causative genes of differences in the prevalence of IOP variation in OAG according to ethnic groups. CONCLUSIONS: Differences in allele frequencies associated with IOP related SNPs between Koreans and other ethnicities were observed, which may explain the high prevalence of OAG with normal IOP predominantly in Koreans and East Asians.

Long-term efficacy and safety of intravenous injection of clonal mesenchymal stem cells derived from bone marrow in five adults with moderate to severe atopic dermatitis.

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is treated with immunosuppressants. However, long-term use of immunosuppressants may cause toxicity and severe side-effects. To confirm the long-term efficacy and safety of clonal mesenchymal stem cell therapy, we performed investigator-initiated clinical trials and long-term observation in five adult patients with moderate to severe atopic dermatitis that was refractory to conventional treatments. The clinical response assessment values such as Eczema Area and Severity Index (EASI) improved significantly at 16 weeks, and 80% (4/5) of the patients achieved EASI-50 after one or two treatment cycles. Patients were observed for long-term efficacy and safety for an average of 38 weeks (range, 16-86) and showed no serious side-effects. Among the cytokines tested, CCL-17, interleukin (IL)-13, and IL-22 significantly decreased at the end-point of the five participants, two patients who maintained good clinical response over 84 weeks showed increased IL-17 cytokine levels in the blood.

Evolutionary processes of melanomas from giant congenital melanocytic nevi.

Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi-region whole-exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.