Integrated Analysis of Somatic DNA Variants and DNA Methylation of Tumor Suppressor Genes in Colorectal Cancer.

DNA methylation of tumor suppressor genes in cancer is known to be a mechanism for silencing gene expression, but much remains unknown about its extent and relationship to somatic variants at the DNA sequence level. In this study, we comprehensively analyzed DNA methylation and somatic variants of all gene regions across the genome of the major tumor suppressor genes, , , , and mismatch repair genes in colorectal cancer using a novel next-generation sequencing-based analysis method. The Targeted Methyl Landscape (TML) shows that DNA hypermethylation patterns of these tumor suppressor genes in colorectal cancer are more complex and widespread than previously thought.

Establishment of a human induced pluripotent stem cell line, KMUGMCi009-A, from a patient bearing a missense mutation in the MED12 gene leading X-linked Ohdo syndrome.

X-linked Ohdo syndrome is a heterogenous group of disorders characterized by intellectual disability and typical facial features including blepharophimosis. The X-linked Ohdo syndrome is caused by a loss-of-function mutation in the MED12 gene on the X chromosome. The peripheral blood mononuclear cells from a patient carrying missense mutation in the MED12 gene were reprogrammed using the CytoTune-iPS2.

Establishment of a human induced pluripotent stem cell line, KMUGMCi008-A, from a patient with A Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome bearing heterozygous frameshift mutation in the KAT6B gene.

Ohdo syndrome Say-Barver-Biesecker-Young-Simpson (SBBYS) variant is a rare autosomal dominant disorder characterized mainly by intellectual disability, developmental delays, contractures of the knees and hips contractures, thyroid dysfunction, and dysmorphic appearance. The Ohdo syndrome SBBYS variant is caused by heterozygous loss of function mutation in the KAT6B gene. The peripheral blood mononuclear cells from a patient carrying heterozygous frameshift mutation of the KAT6B gene were reprogrammed using the CytoTune-iPS2.

Flexible Integrated Air Pressure Sensors for Monitoring Positive and Negative Pressure Distribution.

Barometric pressure monitoring typically depends on conventional rigid microelectromechanical systems (MEMS) for single-point measurements. However, applications such as fluid dynamics require mapping barometric pressure distribution to study phenomena such as pressure variations on an aircraft wing during flight. In this study, we developed a mechanically flexible, multichannel air pressure sensor sheet using laser-induced graphene (LIG).

Investigation of a novel PROS1 splicing variant in a patient with protein S deficiency.

Here, we report a novel PROS1 splicing mutation in a patient with type I protein S deficiency. Qualitative and quantitative analysis of pathogenic splicing variants at the mRNA level was performed by long-range PCR-based targeted DNA and RNA sequencing. A base substitution in the exon 4 splicing donor site activates a potential splicing donor site in intron 4, resulting in an in-frame insertion of 48 bases (16 amino acids).

Comparison of RNA-Sequencing Methods for Degraded RNA.

RNA sequencing (RNA-Seq) is a powerful technique and is increasingly being used in clinical research and drug development. Currently, several RNA-Seq methods have been developed. However, the relative advantage of each method for degraded RNA and low-input RNA, such as RNA samples collected in the field of clinical setting, has remained unknown.

Qualitative and quantitative analysis of MED12 c.887G>A causing both missense and splicing variants in X-linked Ohdo syndrome.

The phenotypes associated with MED12 pathogenic variants are diverse. Male patients usually have missense variants, but the effects of base substitutions on mRNA splicing have not been investigated. Here, we report a Japanese brother with intellectual disability, characteristic facial appearance with blepharophimosis, cleft palate, Fallot tetralogy, vesicoureteral reflux, and deafness.

Establishment of a human induced pluripotent stem cell line, KMUGMCi010-A, from a patient with X-linked Ohdo syndrome bearing missense mutation in the MED12 gene.

X-linkded Ohdo syndrome is characterized mainly by intellectual disability, delays in reaching development, feeding difficulties, thyroid dysfunction, and dysmorphic appearance with blepharophimosis, immobile mask-like face and bulbous nose. The X-linked Ohdo syndrome is caused by loss of function mutation in MED12 gene on X chromosome. The peripheral blood mononuclear cells from a patient carrying missense mutation of the MED12 gene were reprogrammed using the CytoTune-iPS2.

Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment.

Streamlining Genetic Diagnosis With Long-Range Polymerase Chain Reaction (PCR)-Based Next-Generation Sequencing for Type I and Type II Collagenopathies.

In the practice of clinical genetics, gene testing is usually guided by clinical diagnosis. When dealing with rare diseases, it is often necessary to create new test systems. The handling of a gene with a substantial number of exons poses a challenge both in sequential Sanger sequencing for each exon, and in the setup of capture probes to each exon for next-generation sequencing (NGS).

A Case of Von Hippel-Lindau Disease With Recurrence of Paraganglioma and No Other Associated Symptoms: The Importance of Genetic Testing and Establishing Follow-Up Policies.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Catecholamine production by the tumors leads to high blood pressure. Although most PPGLs are benign, some have metastatic potential.

SNP Array Screening and Long Range PCR-Based Targeted Next Generation Sequencing for Autosomal Recessive Disease with Consanguinity: Insight from a Case of Xeroderma Pigmentosum Group C.

Advances in genetic technologies have made genetic testing more accessible than ever before. However, depending on national, regional, legal, and health insurance circumstances, testing procedures may still need to be streamlined in real-world clinical practice. In cases of autosomal recessive disease with consanguinity, the mutation locus is necessarily isodisomy because both alleles originate from a common ancestral chromosome.

Recessive dystrophic epidermolysis bullosa caused by a novel COL7A1 variant with isodisomy.

Recessive dystrophic epidermolysis bullosa is a genetic collagen disorder characterized by skin fragility that leads to generalized severe blistering, wounds, and scarring. In this report, we present a patient with a novel COL7A1 homozygous nonsense variant, c.793C>T p.

An optimized cocktail of small molecule inhibitors promotes the maturation of dendritic cells in GM-CSF mouse bone marrow culture.

Dendritic cells (DCs) are the most potent antigen-presenting cells, playing an essential role in the pathogen and tumor recognition, and anti-tumor immunity, and linking both the innate and adaptive immunity. The monocyte-derived DCs generated by ex vivo culture, have been used for cancer immunotherapy to eliminate tumor; however, the clinical efficacies are not sufficient, and further improvement is essential. In this study, we established a method to generate DCs using small molecule compounds for cancer immunotherapy.

Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.

Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines with human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes. Among the five enrolled patients, two patients completed six doses per course (2-3 × 10 cells per dose), and an interim analysis was performed based on the immune response.

Establishment of human induced pluripotent stem cell lines, KMUGMCi006, from a patient with Tuberous sclerosis complex (TSC) bearing mosaic nonsense mutations in the Tuberous sclerosis complex 2 (TSC2) gene.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by neuropsychiatric symptoms and multiple dysplastic organ lesions, caused by loss of function mutations in either TSC1 or TSC2. The peripheral blood mononuclear cells (PBMCs) from a patient carrying mosaic nonsense mutation of TSC2 gene were reprogrammed using the CytoTune-iPS2.0 Sendai Reprogramming Kit.

Schimmelpenning-Feuerstein-Mims syndrome induced by HRAS Gly12Ser somatic mosaic mutation: Case report and literature review.

Schimmelpenning-Feuerstein-Mims syndrome (SFMS), an epidermal nevus disease, features skin lesions including craniofacial nevus sebaceous and extracutaneous anomalies (e.g. brain, eye, and bone).

Establishment of a human induced pluripotent stem cell line, KMUGMCi007-A, from a patient with prolidase deficiency (PD) bearing homozygous in-frame mutation in the PEPD gene.

Prolidase deficiency (PD) is a rare autosomal recessive disorder characterized mainly by skin lesions of the legs and feet, respiratory infections and mental retardation, and impaired immune system. To date, no effective PD treatment has been developed. The PD case are caused by homozygous mutation in PEPD gene.

The Detection of Immunity against WT1 and SMAD4 of EpCAM Cancer Cells in Malignant Pleural Effusion.

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8 T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms' Tumor 1 (WT1) antigen over the disease course (two points at MPE and 2, two months after MPE1).

Genotype and Phenotype Landscape of 283 Japanese Patients with Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by multiple dysplastic organ lesions and neuropsychiatric symptoms, caused by loss of function mutations in either or . Genotype and phenotype analyses are conducted worldwide, but there have been few large-scale studies on Japanese patients, and there are still many unclear points. This study analyzed 283 Japanese patients with TSC (225 definite, 53 possible, and 5 genetic diagnoses).

Establishment of a human induced pluripotent stem cell line, KMUGMCi005-A, from a patient with Epidermodysplasia verruciformis (EV) bearing homozygous splicing donor site mutation in the TMC8 gene.

Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human beta papillomaviruses and a high rate of progression to squamous cell carcinoma on sun-exposed skin. The majority of EV cases are caused by homozygous mutation in TMC8. The peripheral blood mononuclear cells from a patient carrying homozygous mutation of the TMC8 gene were reprogrammed using the CytoTune-iPS2.

Establishment of a human induced pluripotent stem cell line, KMUGMCi003-A, from a patient with trichothiodystrophy 1 (TTD1) bearing compound heterozygous missense mutations in the ERCC2 gene.

Trichothiodystrophy 1 (TTD1) is a rare, autosomal recessive, multisystem disorder characterized by the sulfur-deficient brittle hair, cutaneous photosensitivity, high risk of skin cancer, psychomotor retardation. TTD1 is caused by homozygous or compound heterozygous mutation in ERCC2 gene. The peripheral blood mononuclear cells (PBMCs) from a patient carrying two heterozygous missense mutations of the ERCC2 gene were reprogrammed using the CytoTune-iPS2.