Whole Exome-Trio Analysis Reveals Rare Variants Associated with Congenital Pouch Colon.

Anorectal malformations (ARM) are individually common, but Congenital Pouch Colon (CPC) is a rare anorectal anomaly that causes a dilated pouch and communication with the genitourinary tract. In this work, we attempted to identify de novo heterozygous missense variants, and further discovered variants of unknown significance (VUS) which could provide insights into CPC manifestation. From whole exome sequencing (WES) performed earlier, the trio exomes were analyzed from those who were admitted to J.

Whole-Exome Sequencing Identifies a Novel Germline Variant in Gene in Familial Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Only 5% of all CRC cases are due to germline mutations in known predisposition genes, and the remaining genetic burden still has to be discovered. In this study, we performed whole-exome sequencing on six members of a Polish family diagnosed with CRC and identified a novel germline variant in the protein tyrosine kinase 7 (inactive) gene (, ENST00000230419, V354M).

Germline Variants of and Predispose to Familial Colorectal Cancer.

Familial colorectal cancer (CRC) is only partially explained by known germline predisposing genes. We performed whole-genome sequencing in 15 Polish families of many affected individuals, without mutations in known CRC predisposing genes. We focused on loss-of-function variants and functionally characterized them.

The Omic Insights on Unfolding Saga of COVID-19.

The year 2019 has seen an emergence of the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease of 2019 (COVID-19). Since the onset of the pandemic, biological and interdisciplinary research is being carried out across the world at a rapid pace to beat the pandemic. There is an increased need to comprehensively understand various aspects of the virus from detection to treatment options including drugs and vaccines for effective global management of the disease.

CXCL8 Signaling in the Tumor Microenvironment.

The tumor microenvironment represents a dynamic and complex cellular network involving intricate communications between the tumor and highly heterogeneous groups of cells, including tumor-supporting immune and inflammatory cells, cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages, adipose cells, and pericytes. Associated with a variety of growth factors, chemokines, cytokines, and other signaling molecules, the interaction between the tumor microenvironment and the tumor cells empowers aggressiveness of tumor by enhancing its survivability. CXCL8 (also known as Interleukin 8), a multifunctional proinflammatory chemokine that was initially classified as a neutrophil chemoattractant, recently has been found to be a key contributor in tumorigenesis.

A Novel Low-Risk Germline Variant in the SH2 Domain of the SRC Gene Affects Multiple Pathways in Familial Colorectal Cancer.

Colorectal cancer (CRC) shows one of the largest proportions of familial cases among different malignancies, but only 5-10% of all CRC cases are linked to mutations in established predisposition genes. Thus, familial CRC constitutes a promising target for the identification of novel, high- to moderate-penetrance germline variants underlying cancer susceptibility by next generation sequencing. In this study, we performed whole genome sequencing on three members of a family with CRC aggregation.

Whole Genome Sequencing Prioritizes , and as Possible Predisposition Genes for Familial Non-Medullary Thyroid Cancer.

Familial inheritance in non-medullary thyroid cancer (NMTC) is an area that has yet to be adequately explored. Despite evidence suggesting strong familial clustering of non-syndromic NMTC, known variants still account for a very small percentage of the genetic burden. In a recent whole genome sequencing (WGS) study of five families with several NMTCs, we shortlisted promising variants with the help of our in-house developed Familial Cancer Variant Prioritization Pipeline (FCVPPv2).

Whole Exome Sequencing Identifies and Genes as Potentially Cancer Predisposing in Familial Colorectal Cancer.

Germline mutations in predisposition genes account for only 20% of all familial colorectal cancers (CRC) and the remaining genetic burden may be due to rare high- to moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer-predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants: a coding variant in APC downregulated 1 gene (, p.R299H) and a non-coding variant in the 5' untranslated region (UTR) of histone deacetylase 5 gene ().

Application of single-cell sequencing technologies in pancreatic cancer.

Pancreatic cancer (PC) is the third lethal disease for cancer-related mortalities globally. This is mainly because of the aggressive nature and heterogeneity of the disease that is diagnosed only in their advanced stages. Thus, it is challenging for researchers and clinicians to study the molecular mechanism involved in the development of this aggressive disease.

A rare large duplication of MLH1 identified in Lynch syndrome.

Background: The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation.

Methods: In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families.

Hypothetical Proteins as Predecessors of Long Non-coding RNAs.

Hypothetical Proteins [HP] are the transcripts predicted to be expressed in an organism, but no evidence of it exists in gene banks. On the other hand, long non-coding RNAs [lncRNAs] are the transcripts that might be present in the 5' UTR or intergenic regions of the genes whose lengths are above 200 bases. With the known unknown [KU] regions in the genomes rapidly existing in gene banks, there is a need to understand the role of open reading frames in the context of annotation.

Host sphingolipids: Perspective immune adjuvant for controlling SARS-CoV-2 infection for managing COVID-19 disease.

Sphingolipids are potent bioactive agents involved in the pathogenesis of various respiratory bacterial infections. To date, several sphingolipid derivatives are known, but S1P (Sphingosine-1-phosphate) and Ceramide are the best-studied sphingolipid derivatives in the context of human diseases. These are membrane-bound lipids that influence host-pathogen interactions.

Cancer Predisposition Genes in Cancer-Free Families.

Familial clustering, twin concordance, and identification of high- and low-penetrance cancer predisposition variants support the idea that there are families that are at a high to moderate excess risk of cancer. To what extent there may be families that are protected from cancer is unknown. We wanted to test genetically whether cancer-free families share fewer breast, colorectal, and prostate cancer risk alleles than the population at large.

Compromised DNA repair is responsible for diabetes-associated fibrosis.

Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative.

Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing.

Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2).

Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways.

Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family.

Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect.

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23.

Chemotherapy-induced peripheral neuropathy: evidence from genome-wide association studies and replication within multiple myeloma patients.

Background: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients.

Methods: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values< 10 were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects that developed CIPN grade 2-4 while controls developed no or sub-clinical CIPN.