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Genomic Medicine Initiative
Bob Nussbaum
SUMMARY
• UCSF-wide interdepartmental, and interdisciplinary effort established and funded by the EVC and SOM Dean, with support of the Chancellor
• Create the infrastructure to allow UCSF to use genomics in translational research, implementation science, clinical trials and clinical care
• Enhance professional education in applied genomics• Harness campus-wide knowledge and experience to
create efficient, knowledgeable teams that serve campus needs
BENEFITS
• Patient Care: Improve diagnostic and therapeutic abilities
• Clinical Research: Create infrastructure that enables our faculty to obtain extramural grant support
• Education: Create a “Clinical Learning System” in which large numbers of faculty and staff can study how to use genomics creatively and effectively in oncology, clinical genetics, prenatal care and neonatology
UCSF Health System: Raise the profile of UCSF by advancing Precision Medicine through innovative use of genomics in clinical care
MAJOR COMPONENTS• Clinical Cancer Genetics Laboratory (Bastian CLIA Lab at MZ)
– Targeted deep sequencing of driver oncogenes for solid and liquid tumors customized to the needs of the UCSF clinical oncology community
- Transcriptome and cell-free DNA analysis
• IHG Genomics Services Laboratory – CLIA approval pending– Whole exome and whole genome analysis for oncology, undiagnosed
disease in NICU, and maternal and fetal medicine
• Collaboration with UCLA Department of Pathology– CLIA-approved whole exome analysis for undiagnosed diseases– Sharing of sequence and variant data files for a joint video signout
• Coursera Course
5Confidential
Genomic Medicine Initiative
Clinical Cancer Genomics Laboratory(CLIA Lab at Mount Zion)
Director: Boris Bastian
Targeted Sequencing: Tumor/Normal Pairs
Phase 1 Goal = Actionable Cancer Genome by Hybrid Capture
Phase 2 Goal = RNASeq, Cell-Free DNA
IHG Genomics Services Laboratory(CLIA-pending Lab at Parnassus)
Director: Pui Kwok
Whole Exome & Genome Sequencing
Phase 1 Goal = Undiagnosed DiseasesPhase 2 Goals = Prenatal and sick NICU
children
Genomic Medicine Initiative: Laboratory Structure - First Initiatives and Expansion
Phase 1
6
• Sequence exons of ~300 oncogenes for mutations and copy number changes • Analyze for select structural rearrangements. • Plan on paired germline/somatic sequencing• Phase 1 assay does not assess epigenetic alterations or transcriptome
Targeted Oncogene Panel
Reporting
Logistics• The test will be orderable in APeX.• Results will be available in APeX in approximately 3-4 weeks.• Patient’s insurance will be billed using CPT codes for targeted panel sequencing• Initial launch subsidized by the Genomic Medicine Initiative
• Findings annotated and reported in APeX.• Annotation to include information on clinical trials or predicted drug responses • Molecular Pathologists interpret results at Tumor Boards.
Clinical Cancer Genetics LaboratoryOverview of the Phase 1 Pipeline
7Confidential
CCGL: Reporting Molecular Oncology Results
Sample of reporting format available from software vendor Syapse – will be viewable in APeX.
8Confidential
CCGL: Software Support for Oncologists
Confidential
Patient consents to data included in GMI
database
Patient Meets Criteria for Sequencing
Sequencing ordered in APeX
Sample acquired: surgery, or pre-existing
sample
Sample prepared by Pathology / Derm Path
Oncology: Targeted Sequencing – Clinical Cancer Genetics Lab
Inherited Diseases: IHG Genomics Services
Lab
Pipeline Processing: Automated
preprocessing, variant calling, annotation
Clinical Data Input: Tumor Size, Tissue
Type, etc, manually input into Syapse
Filtering: Reviewed by Lab Director -
additional clinical annotation in Syapse
Searchable Database in Syapse: all variants
and phenotypes
Molecular Case Review: Discussion in
context of other findings
Clinical Molecular Report: Case signed out by Primary Lab
Director
Delivery to Tumor Board & Ordering MD: Molecular Pathologists
Final Clinical Findings: APeX – searchable
format – phenotype and outcome data
Billing
Biobanking
Genomic Medicine Initiative: Workflow
Updated: 04/28/2014
10
THIS MONTH’S EXOME SIGNOUT WITH UCLA
Nussbaum – 2 patients
Portale – 1 patient
Slavotinek – 1 patient
Alsadeh – 1 patient
Shieh – 2 patients
Fastq and VCF files requested and sent in advance from UCLA
11
COURSERA COURSE
CollaborationsCollaborations
Pathology• Abul Abbas• JP Grenert
Clinical Laboratories/Laboratory Medicine• Tim Hamill • Michael Skehan• Laura van’t Veer• Betty Yalich
Institute for Human Genetics• Steven Brenner• Brad Dispensa• Mark Kvale• Pui Kwok• Neil Risch• Brandon Zerbe
Helen Diller Family Cancer Center• Sorena Nadaf • Eric Small• Barry Taylor
UCLA• Wayne Grody, Stan Nelson, Sam Strom et al.
Teams “On the Ground”
• Boris Bastian• Michael Korn• Heather Pua• Jessica van Ziffle• Iweh Yei• Jon Hirsch (Syapse)
Exome Clinic• Gilberto de Gente• Marta Sabbadini• Elliott Sherr• Joseph Shieh• Anne Slavotinek
Prenatal/Neonatal Applications• Mary Norton
Coursera• Jeanette McCarthy• Bryce Mendelssohn
Administration• Kristen McCaleb• Karen Ely