Summary of genetic alterations in resistant biopsies among patients progressing on ceritinib or alectinib. Summary of genetic alterations in resistant.

Slides:

Advertisements

Similar presentations

Cancer Treatment from the DNA Perspective

Advertisements

CtDNA NGS testing identified a high-level MET amplification (copy number of 53.6 in circulation) (Figure 1A). The test was repeated on a second tube of.

SI-II A SI-II. Expression analysis of bladder cancer functionally active genes and significantly mutated genes. Comprehensive transcriptome profiling of.

CYB561 mutations. CYB561 mutations. The upper part shows the structure of the CYB561 gene, with the positions of the identified mutations indicated. Gray.

Figure Pedigrees of the SCA42 families identified in this study

Dose-escalation patient response.

Unità Clinica di Diagnostica Istopatologica e Molecolare

The New Taxonomy of Metastatic NSCLC and Physician Treatment Based on Pathologic and Molecular Characteristics The New Taxonomy of Metastatic Non-Small.

Clonal evolution of resistance to sequential ALK inhibitor therapy.

Melanoma donor (MD) NK cells are functionally impaired/exhausted.

Nat. Rev. Clin. Oncol. doi: /nrclinonc

Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study Marco Lo Iacono, PhD, Valentina.

Breast cancer. Breast cancer. A, antitumor activity of abemaciclib in a human xenograft model (T47D) of ER-positive, HER2-negative breast cancer. Athymic.

Regional lymph nodes and distal extracranial metastases are not a reliable surrogate for actionable mutation in brain metastases. Regional lymph nodes.

Jessica J. Lin, MD, Lauren L. Ritterhouse, MD, PhD, Siraj M

WES detects a limited number of clinically targetable alterations in patients with advanced cancer. WES detects a limited number of clinically targetable.

Genomic alterations in breast cancer cell line MDA-MB-231.

Genomic alterations in non–small cell lung cancer, breast cancer, and colorectal cancer. Genomic alterations in non–small cell lung cancer, breast cancer,

Emergence of resistance to immune checkpoint blockade is associated with elimination of mutation-associated neoantigens by LOH and a more diverse T-cell.

Moving Care Forward in Advanced NSCLC

Intrinsic and acquired trastuzumab resistance.

Copy-number alterations in an archival breast cancer sample.

Identification of a MEK2 mutation in a melanoma sample resistant to dabrafenib/trametinib. Identification of a MEK2 mutation in a melanoma sample resistant.

A Multicolor FISH Assay Does Not Detect DUP25 in Control Individuals or in Reported Positive Control Cells Yanina Weiland, Jürgen Kraus, Michael R. Speicher

Whole-exome sequencing identifies NF1 mutations in tumors of melanoma patients exhibiting resistance to vemurafenib. Whole-exome sequencing identifies.

Figure 1. Plasma next-generation sequencing (NGS) assay workflow, comparison of variant allelic fraction with ... Figure 1. Plasma next-generation sequencing.

Molecular Analysis of Plasma From Patients With ROS1-Positive NSCLC

Genetic landscape of salivary duct carcinoma.

Educational Objectives

Methods applied in addition

Oncogenic ALK signaling.

Figure Novel compound heterozygous mutation in the COLQ gene causes congenital myasthenic syndrome Novel compound heterozygous mutation in the COLQ gene.

Distribution of podocyte gene mutations in patients with genetic congenital nephrotic syndrome (CNS) and steroid–resistant nephrotic syndrome (SRNS). Distribution.

ALK resistance mutations predict for sensitivity to lorlatinib in patient-derived cell line models of acquired resistance to ceritinib. ALK resistance.

Alteration calling accuracy and concordance with reference platforms.

On the left, Euler-Venn diagram of point mutations detected by lbNGS and ttNGS on matched genes from the same patients; on the right, the percentage of.

VP16-E2 is a more potent transcriptional activator than Gal4-VP16.

Temporal analysis of clonal evolution in typical FL and matched TFL samples. Temporal analysis of clonal evolution in typical FL and matched TFL samples.

Frequent alterations identified and potential actionability.

KIT mutations in GISTs. A, amino acid sequence of KIT exon 11 mutations in clinical GIST biopsies. –, amino acids that are deleted; italicized amino acids,

Correlation of miR-21 expression levels with DEGs in 28 bladder cancer cell lines. Correlation of miR-21 expression levels with DEGs in 28 bladder cancer.

Predictive value of the FGFR3 mutation assay increases with multiple consecutive FGFR3-positive urine samples. Predictive value of the FGFR3 mutation assay.

Saturation analysis and the discovery of actionability of mutational hotspots. Saturation analysis and the discovery of actionability of mutational hotspots.

Plasma and tissue EGFR allele analyses.

Targetable alterations and pathways in TNBCs after NAC

HPV–human protein network map.

Serial chest CT scans of 33-year-old male with lung adenocarcinoma harboring EGFR-KDD documenting response to afatinib and subsequent acquired resistance.

Extraction diagram of candidate genes identified by global expression analysis. Extraction diagram of candidate genes identified by global expression analysis.

Noninvasive detection of acquired MET amplification as a mechanism of afatinib/trastuzumab resistance using cfDNA. Noninvasive detection of acquired MET.

The long tail of mutational hotspots in cancer.

Molecular heterogeneity can drive mixed response and treatment failure in EGC. A, PET images from Patient #4 obtained before treatment and upon disease.

Prevalence of germline T790M.

Location of the ER mutations and frequencies per cohort.

Correlation of PTEN loss in melanoma cells with an immune resistance phenotype. Correlation of PTEN loss in melanoma cells with an immune resistance phenotype.

A and B, two blocks from the original specimen used for TMA demonstrated areas with varying patterns of ALK rearrangement and KRAS mutation status. A and.

Identification of general and tissue-specific essential genes.

Global mutational landscape of the 170 lung adenocarcinoma patients (discovery cohort). Global mutational landscape of the 170 lung adenocarcinoma patients.

Molecular definitions of lung adenocarcinoma subtypes.

No single ALK mutations confer high-level resistance to lorlatinib.

Genetic analysis suggests the presence of four clinically relevant groups of histologically defined anaplastic oligodendrogliomas. Genetic analysis suggests.

Landscape of genomic alterations identified by WES in biopsies of patients with advanced PDAC. Co-mutation plot displaying integrated genomic data for.

Concordance between liquid versus tissue biopsies.

Mutational signature analysis of WES data from patients with advanced PDAC. A, Projection of signatures representing four main mutational processes identified.

Resistance to entrectinib in xenopatient and colorectal cancer cell models carrying NTRK1 translocations. Resistance to entrectinib in xenopatient and.

Detection of BRCA reversion mutations in pretreatment cfDNA and tumor biopsy. Detection of BRCA reversion mutations in pretreatment cfDNA and tumor biopsy.

Mutational load and mutations in the interferon signaling pathway among patients with advanced melanoma with or without response to anti–PD-1 blockade.

High genomic fidelity of SCLC PDX models derived from both CTCs and biopsies. High genomic fidelity of SCLC PDX models derived from both CTCs and biopsies.

A, study design for measuring the feasibility, concordance, and accuracy of a plasma-based cfDNA sequencing test compared with biopsy-based sequencing.

Driver pathways and key genes in OSCC

STK11/LKB1 genetic alterations are associated with shorter progression-free and overall survival with PD-1 blockade among KRAS-mutant LUAC in the SU2C.

Presentation transcript:

Summary of genetic alterations in resistant biopsies among patients progressing on ceritinib or alectinib. Summary of genetic alterations in resistant biopsies among patients progressing on ceritinib or alectinib. Specimens underwent targeted NGS using the MGH NGS assay or the FoundationOne platform. Only genes with at least one genetic alteration detected in resistant specimens are depicted. If a particular gene was not evaluated in a given specimen due to the type of sequencing platform used, it is represented in dark gray. Within this cohort, the most commonly mutated genes were ALK and TP53. Recurrent alterations in other genes were uncommon. In addition, six ceritinib-resistant, patient-derived cell lines underwent NGS using a 1,000-gene panel (see Genotype Assessments in Methods). Genes from this panel are shown if the following criteria are met: (i) a genetic alteration was present in at least one of the patient-derived cell lines, and (ii) the gene was also included in either the MGH NGS or FoundationOne panels. Please see Supplementary Table S11 for a comprehensive assessment of all genetic alterations identified within these cell lines. Justin F. Gainor et al. Cancer Discov 2016;6:1118-1133 ©2016 by American Association for Cancer Research