MMR in mCRPC
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB27287 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Copy number profiling of mCRPC
2020-04-28 | E-MTAB-7326 | biostudies-arrayexpress
Project description:Objectives. Ovarian cancer (OC) is the eighth most common cancer and the eighth most common cause of cancer-related death in women. Identification of pathogenic variants in OC tissues is important to predict treatment response. This study aim to evaluate the mutational profile of a patient cohort, negative for BRCA1/2 germinal mutations and Mismatch Repair (MMR) defects, using next generation sequencing approach on DNA from formalin-fixed paraffin-embedded (FFPE) samples. We used a custom NGS panel, targeting 34 cancer related-genes, and analyzed NGS data to identify somatic and germline mutations in Italian patients affected by primary epithelia ovarian cancer.
2022-12-15 | E-MTAB-11133 | biostudies-arrayexpress
Project description:Informed consent was obtained to collect human mCRPC tissues and generate the patient-derived xenograft tumors as described previously (Labrecque et al., 2019; Nguyen et al., 2017). The study was approved by the University of Washington Human Subjects Division institutional review board (no. 39053). All animal studies were approved by University of Washington IACUC and performed according to NIH guidelines. Molecular characterization of AR+ mCRPC LuCaP PDXs 70CR, 78CR, 81CR, 96CR, 105CR, 136CR and 147CR was previously described (Labrecque et al., 2019; Nguyen et al., 2017). LuCaP PDX 167CR was established from a liver metastasis of 77-year-old Caucasian male who died of abiraterone-, carboplatin- and docetaxel-resistant CRPC. LuCaP 167CR expresses AR, responds to castration and is negative for synaptophysin. PDX cellular morphology recapitulates the original liver metastasis (Supplementary Figure S8A).
2022-04-06 | GSE163220 | GEO
Project description:Background: In ~50% of Lynch syndrome (LS)-suspected patients (also called Lynch-like syndrome, LLS), the causal mechanism for cancer predisposition remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive genetic and epigenetic analysis. Methods: One hundred and fifteen LLS patients harboring MMR deficient tumors and no pathogenic germline MMR gene mutations were included in this study. Mutational analysis of 26 colorectal cancer associated genes was performed by using a customized multigene panel and massively parallel sequencing. Pathogenicity of MMR variants was assessed by mRNA analysis and multifactorial likelihood calculations. Genome-wide methylome analysis was perfomed by using the Infinium HumanMethylation450K BeadChip. Results: The multigene panel analysis revealed the presence of two MMR gene truncating mutations not found in previous analysis. Of a total of 15 MMR variants of unknown significance identified, five - present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes (MSH3, MUTYH, POLD1, APC, EPCAM, BUB1, FAN1, EXO1 or PSM1) were found in 12 probands. Methylome analysis detected one constitutional MLH1 epimutation in an individual diagnosed with CRC at age 42, but no additional differentially methylated regions were identified in LLS compared to LS patients or healthy individuals. Conclusions: In conclusion, the use of an ad-hoc designed gene panel combined with pathogenicity assessment of variants allows the identification of deleterious MMR mutations as well as new LLS candidate genes. Moreover, constitutional epimutations in non-LS-associated genes are not responsible for the MMR-deficient phenotype observed in LLS patients.
2019-03-09 | GSE128067 | GEO
Project description:Background: In ~50% of Lynch syndrome (LS)-suspected patients (also called Lynch-like syndrome, LLS), the causal mechanism for cancer predisposition remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive genetic and epigenetic analysis. Methods: One hundred and fifteen LLS patients harboring MMR deficient tumors and no pathogenic germline MMR gene mutations were included in this study. Mutational analysis of 26 colorectal cancer associated genes was performed by using a customized multigene panel and massively parallel sequencing. Pathogenicity of MMR variants was assessed by mRNA analysis and multifactorial likelihood calculations. Genome-wide methylome analysis was perfomed by using the Infinium HumanMethylation450K BeadChip. Results: The multigene panel analysis revealed the presence of two MMR gene truncating mutations not found in previous analysis. Of a total of 15 MMR variants of unknown significance identified, five - present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes (MSH3, MUTYH, POLD1, APC, EPCAM, BUB1, FAN1, EXO1 or PSM1) were found in 12 probands. Methylome analysis detected one constitutional MLH1 epimutation in an individual diagnosed with CRC at age 42, but no additional differentially methylated regions were identified in LLS compared to LS patients or healthy individuals. Conclusions: In conclusion, the use of an ad-hoc designed gene panel combined with pathogenicity assessment of variants allows the identification of deleterious MMR mutations as well as new LLS candidate genes. Moreover, constitutional epimutations in non-LS-associated genes are not responsible for the MMR-deficient phenotype observed in LLS patients.
2019-03-09 | GSE128064 | GEO
Project description:Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
2022-03-09 | GSE193430 | GEO
Project description:High correlation was observed between T cell responses to SARS-CoV-2 and MMR and Tdap vaccine proteins in infected and uninfected individuals; the overlapping T cell population contained an effector memory T cell subset previously implicated in protective anti-viral immunity and their activation required APC-derived IL-15, known to sensitize T cells to activation. We were able to detect cross-reactive TCR repertoire in antigen experienced T cells recognizing SARS-CoV-2, MMR and Tdap epitopes using clonotyping and scRNA-seq. Indices of disease severity were reduced in MMR or Tdap vaccinated individuals by 32-38% and 20-23% respectively, among 73.582 COVID-19 positive patients.
2021-08-02 | GSE181046 | GEO
Project description:The prognosis of patients with metastatic castration-resistant prostate cancer (mCRPC) is variable. Several blood-related prognostic factors have been reported, including transcriptional profiling of whole blood and neutrophil to lymphocyte ratio. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. Subjects/Patients and Methods: Pre-treatment whole blood samples from chemotherapy-naïve mCRPC patients were prospectively collected before treatment with enzalutamide. The study consisted of a training cohort including 98 patients treated with enzalutamide in a phase 2 biomarker clinical trial (NCT02288936)
2024-08-02 | GSE248619 | GEO