Publications by authors named "Michael P Morrissey"

Liquid biopsy offers a versatile, noninvasive opportunity to diagnose, characterize, and monitor disease in patients with cancer. There are particularly promising applications with which to use liquid biopsies to predict and evaluate response to immunotherapy. Circulating tumor DNA (ctDNA) can reflect the genomic state of a patient's overall disease and, thus, might identify prognostic and predictive biomarkers for immune checkpoint inhibitor therapy.

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Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers.

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Article Synopsis
  • Racial and ethnic disparities in breast cancer mortality are increasing, yet genomic studies often overlook diverse populations, highlighting a gap in research.
  • The study analyzed 194 breast cancer patients from Nigeria alongside 1,037 patients from The Cancer Genome Atlas (TCGA), revealing that Nigerian tumors have distinct genomic features indicating more aggressive cancer biology.
  • Key findings include higher rates of specific mutations in Nigerian patients and the identification of novel genes linked to breast cancer, potentially paving the way for tailored treatments for underrepresented groups.
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Background: Matched sequencing of both tumor and normal tissue is routinely used to classify variants of uncertain significance (VUS) into somatic vs. germline. However, assays used in molecular diagnostics focus on known somatic alterations in cancer genes and often only sequence tumors.

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Mantle cell lymphoma (MCL) is an aggressive malignancy that is characterized by poor prognosis. Large-scale pharmacological profiling across more than 100 hematological cell line models identified a subset of MCL cell lines that are highly sensitive to the B cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin. Sensitive MCL models exhibited chronic activation of the BCR-driven classical nuclear factor-κB (NF-κB) pathway, whereas insensitive cell lines displayed activation of the alternative NF-κB pathway.

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The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines.

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