8215 results for "canc*"

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• Comprehensive analyses of genetic aberrations in gastroenterological tumors

  Intestinal metaplasia (IM) is a risk factor of gastric cancer in gastric mucosa with Helicobacter pylori infection. To explore the susceptibility to the cancer development in pure gastric IM, we investigated landscape of genetic alterations in gastric single-glands with IM.

  Study JGAS000269

• Whole exome sequencing and RNA sequencing of patient-derived pancreas neoplasm organoids

  Pancreatic cancers arise from two different precursors; intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasm (PanIN), while biological differences in cancers originated from them remain obscure. Here, we analyzed their genomic and transcriptomic landscapes using patient-derived organoids.

  Study JGAS000263

• High-coverage whole exome sequence in non-TRU-type lung adenocarcinomas

  In order to elucidate the key genetic events in non-TRU-type lung cancer, we selected 43 non-TRU-type lung adenocarcinomas and performed a whole exome sequence and RNA-seq analysis using a next-generation sequencer. The results of the analysis identified mutations in TP53, KRAS and NKX2-1 as the top three significantly mutated genes, while the EGFR mutation was rare in this cohort. Eight NKX2-1 mutations (5 frameshift, 2 nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1 mutations (missense and frameshift). All NKX2-1 mutants were transcriptionally inactive in reporter assays. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1 mutations (5 cases), while 1 enteric and 1 acinar adenocarcinoma harbored the NKX2-1 mutation.

  Study JGAS000105

• Immunohistochemical and molecular pathological search in gastrointestinal tumors

  Purpose: RSPO fusions are recently identified recurrent genetic alterations in colorectal cancer (CRC), which lead to WNT pathway activation and are potential therapeutic targets. We aimed to investigate the clinicopathological and molecular features of RSPO fusion-positive CRCs. Experimental Design: We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription polymerase chain reaction. RSPO fusion-positive tumors were characterized for their clinicopathological features and subjected to whole exome sequencing (WES). Results: Our analysis identified 29 CRCs with RSPO fusions (2.8%), consisting of 5 with an EIF3E-RSPO2 fusion and 24 with PTPRK-RSPO3 fusions. The patients were 17 females and 12 males with the median age of 64 years. Thirteen tumors were located in the right colon, 8 were in the left colon, and 8 were in the rectum. Histologically, most of the tumors (24/29, 83%) were classified as adenocarcinomas, not otherwise specified. However, about half of the tumors (13/29, 45%) had a focal or extensive mucinous component, which is significantly more frequent compared with RSPO fusion-negative tumors (13%; p = 8.1 �� 10-7). Four tumors (14%) were mismatch repair-deficient, three of which were associated with MLH1 promoter methylation. WES identified KRAS, BRAF, and NRAS mutations in a total of 27 cases (93%). In contrast, pathogenic mutations in major WNT pathway genes other than RSPO fusions were virtually absent. The presence of an RSPO fusion tended to show shorter overall and recurrence-free survivals in stage II and III patients although the differences were not significant. Conclusions: RSPO fusion-positive CRCs constitute a rare subgroup of CRCs with several characteristic clinicopathological and genetic features. The mutual exclusivity with other WNT pathway gene alterations supports RSPO fusions as valid therapeutic targets in CRC.

  Study JGAS000538

• Analytical study of protein function and RNA expression involved in predicting treatment efficacy and adverse event development in lung cancer radiotherapy.

  The purpose of this study is to elucidate the functions of DNA repair proteins and RNA expression that are involved in the therapeutic efficacy and adverse events of radiotherapy for lung cancer at our hospital. In particular, this is an exploratory study to identify proteins and RNAs involved in the expression of proteins that are likely to be involved in the prediction of radiotherapy response and adverse events.

  Study JGAS000545

• CRISPR-screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

  Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated NSCLC and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 �� TNO155, alone or combined with the PI3K�� inhibitor alpelisib and/or the CDK4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition.

  Study JGAS000643

• Genomic features of Helicobacter pylori-na��ve diffuse-type gastric cancer.

  Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-na��ve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-na��ve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-na��ve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-na��ve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP- exposed DGCs; 1.97 [0.48���7.19] and HP-na��ve DGCs; 1.09 [0.38���3.68] per megabase; p=0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p<0.0001). CDH1 was mutated at similar frequencies in both groups, whereas RHOA���ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p=0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p<0.0001), 7p (p=0.0035) and 7q (p=0.0354), and losses in 16q (p=0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p<0.0001) and CDX2 (p=0.0002) and a lower expression of the gastric marker, MUC5AC (p=0.0305) among HP-exposed DGCs. HP-na��ve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-na��ve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings.

  Study JGAS000575

• Development of molecular targeted therapy for small cell lung cancer by comprehensive genome analysis

  Aims: Identifying new therapeutic targets of small cell lung cancer (SCLC), genome-wide mutation analysis has been performed. Methods: Genomic DNA was extracted from formalin-fixed or methanol-fixed tissue samples. 71 Mb of DNA fragments containing whole coding exons were concentrated using SureSelect Human All Exon V4+UTRs Kit (Agilent Technologies) followed by 100-bp paired end sequencing by HiSeq 2000 (Illumina). Participants/Materials: 51 of 1042 cases of pathologically diagnosed small seen lung cancer that were registered to National Cancer Hospital East Lung Cancer Database in 1992-2012, and which surgically resected or biopsy samples were suitable for DNA extraction for further analyses.

  Study JGAS000037

• Project for Development of Innovative Research on Cancer Therapeutics; Identifiying the predictive factors for response to chemoherapy in ovarian cancer

  To identify novel predictive biomarkers of response to chemotherapy for clear cell carcinoma of the ovary

  Study JGAS000076

• Project for Development of Innovative Research on Cancer Therapeutics;Shuttle system between petient-derived xenograft and ex vivo culture for innovative platform of evaluating drug sensitivity.

  We developed CTOS (cancer tissue-originated spheroid) panel covering diversity among patients for colorectal cancer, lung cancer and cervical small cell carcinoma. We then carried out exome sequence analysis of tumor tissues, cell lines and CTOS derived from patients to validate qualitative changes in preparation, culture, cell line, transplantation and passage of CTOS pathologically, biochemically, molecular biologically.

  Study JGAS000089