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1. Genetics and management of inherited cancer predisposition 1
- Prof. Joshua Schiffman
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2. Genetics and management of inherited cancer predisposition 2
- Prof. Joshua Schiffman
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3. The cytogenetics of childhood acute leukemia
- Dr. Susana C. Raimondi
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4. Chromosome translocations and cancer
- Prof. Felix Mitelman
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5. Acute myeloid leukemia: genetics, prognosis and treatments
- Prof. Stephen Nimer
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6. Genetic abnormalities in acute lymphoblastic leukemia
- Prof. Ching Hon Pui
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7. Molecular genetics of non-Hodgkin lymphoma
- Prof. Jude Fitzgibbon
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8. Genetics of breast and ovarian cancer
- Prof. Jeffrey Weitzel
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9. The genetics and genomics of familial renal carcinoma
- Prof. Eamonn Maher
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10. Genomics of lung cancer
- Prof. Ramaswamy Govindan
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11. The genetics of glioblastoma
- Dr. Hai Yan
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12. Genetics of tumor metastasis 1
- Prof. Robert Weinberg
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13. Genetics of tumor metastasis 2
- Prof. Robert Weinberg
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14. CML: genetic paradigm of targeted therapy 1
- Prof. Michael W. Deininger
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15. CML: genetic paradigm of targeted therapy 2
- Prof. Michael W. Deininger
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16. The non-coding RNA revolution in the cancer society
- Prof. George Calin
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17. Role of molecular markers in guiding therapy in cancer
- Prof. Joe Duffy
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18. Functional cancer genomics
- Prof. Roderick Beijersbergen
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19. Pharmacogenomics in cancer therapy
- Prof. Sharon Marsh
Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Acknowledgments
- Genetic alteration: example
- Non-small cell lung cancer: EGFR inhibition (1)
- Non-small cell lung cancer: EGFR inhibition (2)
- Non-small cell lung cancer: EGFR inhibition (3)
- ALK positive non-small cell lung cancer
- ROS1 NSCLC: effect of Crizotinib
- EGFT-TK inhibitor early studies
- Histological distribution of lung cancer
- Talk outline
- Ethical aspects of genome sequencing
- Genomic landscape of lung cancer
- Mutational burden
- Circos plot
- Mutational burden of smoker vs. non-smoker
- Global mutational spectrum of SCLC
- CDKN2A: loss of function mechanisms
- Chromothripsis
- Molecular subtypes
- Squamous cell lung cancer subtypes
- Squamous cell carcinoma: mRNA expression
- Lung adenocarcinoma (LUAD): pre-invasive lesions
- LUAD: invasive adenocarcinoma
- Expression subtypes: LUAD
- LUAD subtypes: TCGA
- LUAD subtypes: prognostic significance
- Patterns of mutation in specific genes
- Altered pathways
- Pathway alterations in squamous cell cancer
- Lung adenocarcinoma: key pathways altered
- Lung adenocarcinoma: MAPK pathway
- Lung adenocarcinoma: PI3K pathway
- Biologically relevant mutated genes in SCLC
- Therapeutic implications (targeted therapies)
- Significantly mutated genes in SCLC
- Adenocarcinoma mutation frequencies
- Previously oncogene-negative group
- Translocation partners of FGFR
- Oncogenic NTRK1 rearrangements
- Fusion genes
- Drivers and targets in SCLC
- Umbrella vs. basket studies
- Databases: 'DGIdb' and' My Cancer Genome'
- Intratumoral heterogeneity (clonal evolution)
- Intertumor, clonal & intratumor heterogeneity
- Multi clonal & mono clonal tumors
- Spatial heterogeneity of non-silent mutations
- Evolutionary trajectories of tumors
- The illusion of clonality in a single biopsy
- Clonal evolution as indicator of prognosis
- Initial tumor vs. metastasis
- Emerging areas of research
- TCGA lung cancer project status report
- 10,000 samples required to have 90% power
- ALCHEMIST
- Evolution of pre-cancer
- Clonal evolution and disease progression
- Cancer and immune system immunoediting
- Immunoediting studies
- Long intergenic non-coding RNAs
- Lung cancer susceptibility gene(s) discovery
- Genomics of lung cancer (Lessons learned)
Topics Covered
- Complexity of the lung cancer genome
- Molecular classification of subtypes
- Pathways of activation in tumors
- Intratumoral heterogeneity
- Targetable alterations in patients
- Emerging areas in genomics of lung cancer
Talk Citation
Govindan, R. (2016, January 31). Genomics of lung cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 12, 2024, from https://doi.org/10.69645/ZDYF9546.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Ramaswamy Govindan, Consultant: Celgene, Bayer, Roche, GSK, Clovis, BI, Genentech Speaker's Bureau: Baxalta, Roche Grant/Research Support (Principal Investigator): K12; R25
A selection of talks on Oncology
Transcript
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0:00
Hello, I am Ramaswamy Govindan,
a medical oncologist at
the Washington University School
of Medicine in St. Louis.
I'm an expert in lung cancer and
cancer genomics.
Today we are going to talk about
the genomics of lung cancer.
0:17
I have no conflicts relevant
to this presentation.
I'm a consultant for BMS, BI,
Pfizer, Mallinckrodt Medical,
Genentech, Novartis, and GlaxoSmithKline.
0:30
I want to acknowledge the investigators
from the Cancer Genome Atlas project.
I specifically want to thank Dr.
Matthew Meyerson and Dr.
Steve Baylin, my two co-chairs,
for their support.
I also want to thank my colleagues at the
Washington University School of Medicine,
specifically those at the Genome
Institute, Dr. Richard Wilson, Dr.
Elaine Mardis, and Dr.
Li Ding, for their collaboration.
0:56
I want to begin with a story.
This is a patient of mine with
advanced non-small cell lung cancer,
who came to see me after receiving
multiple lines of chemotherapy.
When we saw her,
she had advanced disease and
she had a lot of symptoms related to her
cancer, she was unable to work full-time.
We biopsied her tumor, as you can
see here she has a fairly large and
impressive tumor on the right side.
The biopsy showed a 12 base-pair
insertion in exon 20 of the ERBB2 gene.
This is a known oncogenic alteration
seen in a small number of patients
with non-small cell lung cancer.
When we treated her as a part of
the phase 1 study with neratinib and
temsirolimus, she had an impressive
response, as you can see here,
from before to after treatment, she had
a very nice decrease in the tumor size and
had significant benefit clinically
as well as radiographically.
She in fact went back to work full-time,
and worked for nearly a year before
the cancer progressed, she's now
currently on salvage chemotherapy but
she had a very good one year with
the combination of neratinib and
temsirolimus, because of
the recognition that her tumor had this
activating mutation in the ERBB2 gene.