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

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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

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• 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

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CCGL: Reporting Molecular Oncology Results

Sample of reporting format available from software vendor Syapse – will be viewable in APeX.

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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

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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

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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