KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Targeting Ferroptosis to Iron Out Cancer.

Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms of RCD have been identified and are increasingly being implicated in various human pathologies. Here, we critically review the current state of the art regarding non-apoptotic types of RCD, including necroptosis, pyroptosis, ferroptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis and oxeiptosis. The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.

https://biblio.ugent.be/publication/8616364/file/8616366.pdf

The molecular machinery of regulated cell death

Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down’s syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)

/pdf/chromosomal-microarray-versus-karyotyping-for-prenatal-2g04y46gru.pdf

Chromosomal microarray versus karyotyping for prenatal diagnosis

https://www.cell.com/cell/pdf/S0092-8674(15)00699-6.pdf

Elucidating Compound Mechanism of Action by Network Perturbation Analysis

Background: Recently identified genetic variants from genome-wide association studies (GWAS) on breast cancer have not been validated in Asian populations, except in China. In this study, we sought to confirm the association between known variants and breast cancer in Korean women and further evaluate the associations of individual single nucleotide polymorphisms (SNP) with different intrinsic subtypes of breast cancer.

Methods: In total, 3,321 invasive breast cancer patients and 3,500 healthy controls were genotyped for five SNPs by using the TaqMan assay. The SNPs genotyped included rs2046210 (6q25.1), rs2981582 ( FGFR2 ), rs889312 ( MAP3K1 ), rs3803662 ( TOX3 / TNRC9 ), and rs4973768 ( SLC4A7 ). Tumors were classified into four intrinsic subtypes based on estrogen receptor (ER), progesterone receptor, HER2, and Ki67 expression.

Results: All five SNPs were significantly associated with risk of breast cancer in dominant, recessive, and additive models. ORs per risk allele (95% CI) were 1.29 (1.16–1.43), 1.40 (1.18–1.68), 1.22 (1.06–1.41), 1.52 (1.30–1.77), and 1.20 (1.08–1.33) for rs2046210, rs2981582, rs889312, rs3803662, and rs4973768, respectively. A multigene logistic regression risk model was generated with the SNPs. In subtype analysis, all 5 SNPs were associated with the Luminal A subtype. Two SNPs (rs2046210 and rs3803662) were linked to the ER−HER2+ subtype, and only rs2046210 SNP was associated with the triple-negative subtype.

Conclusions: The five SNPs from GWAS were significantly associated with breast cancer risk in Korean women. Associations were heterogeneous according to the intrinsic subtype of breast cancer.

Impact: Our result is an important contribution to the literature about genetic susceptibility for breast cancer in nonwhite populations. Cancer Epidemiol Biomarkers Prev; 20(5); 793–8. ©2011 AACR .

https://cebp.aacrjournals.org/content/cebp/20/5/793.full.pdf

Common Genetic Variants Associated with Breast Cancer in Korean Women and Differential Susceptibility According to Intrinsic Subtype

women and differential susceptibility according to intrinsic subtype

Osteoclastogenesis involves the commitment of macrophage-lineage precursors to tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear pre-osteoclasts (pOCs) and subsequent fusion of pOCs to form multinuclear mature osteoclasts. Despite many studies on osteoclast differentiation, little is known about the signaling mechanisms that specifically mediate the osteoclastic commitment. In this study, we found that inhibition of JNK at the pOC stage provoked reversion of TRAP(+) cells to TRAP(-) cells. The conversion to TRAP(-) cells occurred with concomitant return to the state with higher expression of macrophage antigens, and greater activity of phagocytosis and dendritic-differentiation potential. JNK inhibition at the pOC stage reduced NFATc1 and CaMK levels, and addition of active NFATc1 partially rescued the effect of JNK inhibition. In addition, the level of NFATc1 was decreased by knockdown of CaMK by RNAi and by catalytic inhibition of CaMK, which both caused the reversion of pOCs to macrophages. These data suggest that JNK activity is specifically required for maintaining the committed status during osteoclastogenesis and that the CaMK-NFATc1 pathway is the key element in that specific role of JNK.

/pdf/the-jnk-dependent-camk-pathway-restrains-the-reversion-of-vax77rri4m.pdf

The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation

While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies. We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray™ M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping. In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis. We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically-uncertain genomic regions.

/pdf/application-of-a-target-array-comparative-genomic-4jflzysv5c.pdf

Jung Hoon Woo

Papers

Elucidating Compound Mechanism of Action by Network Perturbation Analysis

Common Genetic Variants Associated with Breast Cancer in Korean Women and Differential Susceptibility According to Intrinsic Subtype

women and differential susceptibility according to intrinsic subtype

The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation

Application of a target array comparative genomic hybridization to prenatal diagnosis.