Is there a single path to HCC?

1
Is there a single path to HCC?

• Jessica Zucman-Rossi
• Inserm U674  Functional genomic of solid
  tumors 
• 27 rue Juliette Dodu, Paris
• zucman_at_cephb.fr

2
Natural history of hepatocarcinogenesis
HCV
Chronic hepatitis
HBV
AFB1
Small cell dysplasia Macroregenerative nodules
Alcohol
hemochromatosis
Cirrhosis
HCC
Oral contraception
Liver cell adenoma
Glycogen storage
Androgen
Risk Pré-neoplastic Malignant factors
steps transformation
3
Genetic alterations in hepatocarcinogenesis
HCC
Normal liver
Small cell dysplasia
Cirrhotic nodules

• Oncogene
• activation
• tumor suppressor gene inactivation

70
30-50
Monoclonality
10-30
Chromosome imbalance
4
Main pathways altered in hepatocarcinogenesis
ß-caténine mutation Axine1 mutation 20-35 des CHC
P53 mutation P14 25-50 of HCC
P53
Wnt
Mutation, methylation RB1
Rb
CDKN2A P16
Gankyrin
IGF2R mutation IGF2 hyperexpression
TGFß
Jak-Stat
SOCS1 methylation
Ras
K-ras, Nras, Hras mutation
HNF1a
TCF1 Mutation
5
Genetic alterations define two mechanisms of
hepatocarcinogenesis
Laurent-Puig et al, Gastroenterology, 2001