1. Genomic Medicine Initiative
Bob Nussbaum

2. 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

3. 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

4. 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

5. Confidential
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 Diseases
Phase 2 Goals = Prenatal and sick NICU
children
Genomic Medicine Initiative:
Laboratory Structure - First Initiatives and Expansion
5
Phase 1

6. 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 Laboratory
Overview of the Phase 1 Pipeline

7. 7
Confidential
CCGL: Reporting Molecular Oncology
Results
Sample of reporting format available from software vendor Syapse – will be viewable in APeX.

8. 8
Confidential
CCGL: Software Support for Oncologists

9. 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
10
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
11

12. Collaborations
Collaborations
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