title: Personalized oncogenomics: clinical experience with malignant peritoneal mesothelioma using whole genome sequencing.
abstract: Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants) and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease.
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Brandon S
authors: BS
authors: Sheffield
authors: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver Centre, Vancouver, Canada.
authors: Anna V
authors: AV
authors: Tinker
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors: Yaoqing
authors: Y
authors: Shen
authors: PhenoPath Laboratories, Seattle, Washington, United States of America.
authors: Harry
authors: H
authors: Hwang
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Hector H
authors: HH
authors: Li-Chang
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors: Erin
authors: E
authors: Pleasance
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors: Carolyn
authors: C
authors: Ch'ng
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Amy
authors: A
authors: Lum
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Julie
authors: J
authors: Lorette
authors: University of British Columbia, Department of Surgery, Surgical Oncology, Vancouver, Canada.
authors: Yarrow J
authors: YJ
authors: McConnell
authors: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver Centre, Vancouver, Canada.
authors: Sophie
authors: S
authors: Sun
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors: Steven J M
authors: SJ
authors: Jones
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada; PhenoPath Laboratories, Seattle, Washington, United States of America.
authors: Allen M
authors: AM
authors: Gown
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: David G
authors: DG
authors: Huntsman
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: David F
authors: DF
authors: Schaeffer
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Andrew
authors: A
authors: Churg
authors: University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada.
authors: Stephen
authors: S
authors: Yip
authors: British Columbia Cancer Agency, Division of Medical Oncology, Vancouver Centre, Vancouver, Canada.
authors: Janessa
authors: J
authors: Laskin
authors: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
authors: Marco A
authors: MA
authors: Marra
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D016515:Genes, Neurofibromatosis 2; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000235:genetics*; D057285:Precision Medicine; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases