Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to define NSCLC and the potential of genomics (part 2)
•
4 likes•1,164 views
![[object Object],Males Females Current smokers in France IARC 2008; INSERM 2007 Sun S et al, Nature Can Rev 2007 32 % 21% 15 Millions people CANCER France Europe World Incidence Mortality Prevalence 320 000 144 000 800 000 2 600 000 1 600 000 8 000 000 12 000 000 7 600 000 28 000 000](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to define NSCLC and the potential of genomics (part 2)
Similar to Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to define NSCLC and the potential of genomics (part 2) (20)
More from European School of Oncology
More from European School of Oncology (20)
Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to define NSCLC and the potential of genomics (part 2)
- 1. Gene Profiling in Clinical Oncology 8-9 April 2011 Viareggio, Italy New markers to define NSCLC and the potential of genomics L.Lacroix PharmD PhD Institut Gustave Roussy, Villejuif, FR Friday, 8 April 2011
- 4. Patient background heterogeneity Tumor molecular heterogeneity Cancer is a gene disease
- 7. Goals of tailoring therapy according to predictive markers Other treatments Gandara R, et al. J Clin Oncol, 2007: Abst 7500 Responders with standard therapy Non responders Toxicity Patients with same diagnosis Improve therapy
- 17. Mutations FISH Hirsch, J Clin Oncol 2006 Response biomarkers
- 19. IPASS study (Mok TS et al. NEJM 2009)
- 22. Engelmann et al. 2006 Bean et al. PNAS 2007 In resistant tumors 9/43 (21%) Met amplification 20/43 (47%) T790M (4 with Both ) (In Naïve tumor 2/62 (3%) Met Amp and 0/62 T790M )
- 44. 33% unknown or unfrequent abnormalities pangenomic analysis Unknown therapeutic impact Xxx? markers (FISH/Mut°) 33% Trials 3 markers EGFR/KRAS/ALK Approval or Trials 33%
- 51. Subramanian & Simon JNCI 2010 Chen, et al NEJM, 2007 Lau SK, et al JCO, 2007 Stg IA Stg IB Stg IA Stg IB 3 years survival among groups Validation of 5 genes and 3 genes signature on Shedden et al. large data set
Editor's Notes
- 10 septembre 2006
- 10 septembre 2006
- Lung cancer pathogenesis is also quite complicated through multiple molecular pathways destined to develop invasive NSC or SC lung cancer. Just example about 10 %of lung cancer patients comes from non-smokers through mutation of EGFR and rather small fraction of Adenocarcinoma preceded by AAH through RAS mutation and also rather large fraction of Adenoca comes from without clear preneoplastic lesions that is quite perplexing. And also squamous cell carcinoma can be preceded by bronchial dysplasia and /or angiogenesis and chronic inflammation through COPD. Finally mutation of P53 and other multiple genetic changes progress to develop small cell cancer
- 10 septembre 2006
- 10 septembre 2006
- 10 septembre 2006
- Molecular analysis of EML4-ALK breakpoints The break-apart FISH assay detects disruption of the ALK locus but it does not confirm that EML4 is the partner fusion gene. Therefore, RT-PCR was used to analyze the exon breakpoints in 31 ALK FISH-positive cases. Using this technique, the most frequently identified genotype was exon 13 of EML4 fused to exon 20 of ALK. This was present in 12 out of 29 cases or 41%. (Note that two cases failed the analysis.) Other breakpoints included EML4 at exon 6, alternative exon 6b, exon 18, and exon 20. An EML4-ALK fusion transcript could not be identified in nine cases, suggesting that either alternative EML4 exons were involved or that EML4 was not the ALK fusion partner. Unfortunately, there were insufficient data to correlate EML4-ALK breakpoint with smoking history or response rate. One heavy smoker among the responding patients, No obvious correlation between IHC ALK expression signal (last row), ALK positivity by FISH, breakpoint and clinical outcome
- 10 septembre 2006
- Les premières grosses études datent des années 2001 avec la publication de 3 grosses cohortes (Harvard_Bhattacharjee/Stanford_Garber/Michigan_Beer) Ces premières études montrent une bonne concordance entre les types histologiques (SCLC/ADC/Ep./Norm…) On note également l’existence de sous groupes moléculaires pour le ADC.
- De nombreuses études ont été publiés à partir de ré-analyse des données précédemment citées. Une métanalyses de données des ces 3 études permet de pooler tout les résultats. En comparant les profils d’expression des gènes on peut rapprocher chaque groupe d’un autre type histologique.
- De plus ces groupes présentent des pronostics différents , plus particulièrement pour les stades I/II.
- Hétérogénéité tumorale : zones de nécroses, de tissus normal et parfois tumeurs mixte (ADK+SCC ou CBNPC + CPC…) ; d’où l’importance d’une vision ‘globale’ de la tumeur Les différentes techniques ont des impératifs de ‘minimum tissulaire’ pour être réalisée. Lorsque le diagnostic est porté par cytologie, peu d’études complémentaires pourront être proposées. Le Fixateur Bouin a été beaucoup utilisé en France, il l’est de moins en moins. Il colore les tissus en jaune car il contient, en plus du formol, de l’acide picrique qui endommage l’ADN+++ et inhibe les enzymes utilisé dans les réactions de PCR. Les études de biologies moléculaires sont alors difficiles ou impossibles.