11769 results for "cancer rna-seq"

in 14.98 milliseconds.

• Integration of genomics and histology reveals diagnosis and effective therapy of refractory cancer of unknown primary with PDL1 amplification (H021)

  Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multi-agent chemotherapy. Molecular profiling within a clinical whole-exome and transcriptome sequencing program revealed a heterozygous, highly amplified KRAS G12S mutation, compound-heterozygous TP53 mutation/deletion, high mutational load, and focal amplification of chromosomes 9p (including PDL1 [CD274] and JAK2) and 10p (including GATA3). Integrated analysis of molecular data and conventional histopathology suggested a diagnosis of triple-negative breast cancer (TNBC) and provided a rationale for immune checkpoint inhibitor therapy with pembrolizumab, which resulted in rapid clinical improvement and a lasting partial remission. Analysis of 157 TNBC samples from The Cancer Genome Atlas revealed focal, high-level PDL1 amplification coinciding with excessive PDL1 mRNA expression in 24% of cases. Collectively, these results illustrate the diagnostic utility of multidimensional tumor profiling in cases with non-descript histology and immune phenotype, demonstrate the predictive power of genomic PDL1 amplification for immune checkpoint inhibition, and suggest a targeted therapeutic strategy in chromosome 9p24.1/PDL1-amplified cancers.H021

  Study EGAS00001001846

• Defining the metastasome in colorectal cancer: Implications for hypotheses on metastasis evolution and personalized therapy (HIPO-032)

  Personalized cancer therapy aims at individual genetic changes characterizing primary cancers. Still, however, metastasis is the major clinically unmet problem, also due to an incomplete understanding of its molecular evolution.This study is the first to define the metastasis-specific whole genome landscape of human colorectal primary vs. matched metastatic lesions.Protein coding, ncRNA genes and 3’UTRs harbored about a third each of single nucleotide variations (SNVs)/indels, 19% of them being metastasis-specific. We found novel mutational hills among ncRNAs and 3’UTRs, copy number changes able to explain changes in microRNA expression in metastases, and novel metastasis-specific mutations in the 3’UTRs on important cancer signalling genes. Some metastatic lesions showed targetable mutations not detected in the primaries. Analysis of mutual exclusivity patterns supported a model that has progressive alterations in important colorectal cancer genes and revealed new partners. Metastatic lesions were enriched in SNVs, specific structural variations, and alterations in genes affecting cell adhesion and extracellular matrix interaction.Furthermore, a hepatic stellate activation cascade was enriched in metastases, suggesting genetic programs for site-specific colonization. Allele frequency distribution and mutational signature analysis suggests a common ancestor clone to both the primary tumor and the metastasis, with additional mutagenesis ongoing in both sites independently. Taken together, our results significantly add to hypothesis generation on metastasis evolution, and suggest novel metastasis-specific genomic changes which would be missed by current personalized therapy concepts. (HIPO-032)

  Study EGAS00001002717

• The Institute of Cancer Research - Endocrinology Team

  Dac EGAC00001000532

• CRMY-Translational Cancer Biology Research Unit DAC

  Dac EGAC00001003199

• MD Anderson Cancer Center Data Access Committee

  Dac EGAC00001002802

• Radboud Pediatric Cancer Data Access Committee

  Dac EGAC00001000369

• Genetic predisposition to cancer, University of Tampere

  Dac EGAC00001000488

• Cancer Pharmacogenetics Group at King's College London

  Dac EGAC00001000795

• Colorectal Cancer Organoids Data Access Committee

  Dac EGAC00001000998

• SNP array datas of "Matched" cancer/PNE

  Dac EGAC00001001069

• Korean Advanced Thyroid Cancer Data Access Commitee

  Dac EGAC00001001151

• Gastric Cancer Pan-genome Data Access Commitee

  Dac EGAC00001001211

• DAC for HSTCL study. National Cancer Centre Singapore.

  Dac EGAC00001001302

• DAC for MEITL study. National Cancer Centre Singapore.

  Dac EGAC00001001323

• Prostate Cancer Biobank Insbruck DAC

  Dac EGAC00001001463

• DAC for Phylogenetic reconstruction of breast cancer

  Dac EGAC00001001572

• Children's Cancer Therapy Development Institute DAC

  Dac EGAC00001001581

• DAC for Stuttgart Breast Cancer Cohort

  Dac EGAC00001001693

• Data access committee for lung cancer

  Dac EGAC00001001942

• 4C Ovarian Cancer Data Access Committee

  Dac EGAC00001001953

• Breast Cancer Single-Cell Data Access Committee

  Dac EGAC00001002160

• AA/UTUC Cancer Data Access Commitee

  Dac EGAC00001002162

• Breast Cancer Single-Cell Data Access Committee

  Dac EGAC00001002291

• MDACC Breast Cancer MoonShot Data Access Committee

  Dac EGAC00001002362

• Laboratory of Applied Cancer Genomics team

  Dac EGAC00001002546