基因的差异表达.ppt

Sarcomas with Aberrant Transcription Factors: Biology and Expression Profiling
Marc Ladanyi
Memorial Sloan-Ketteringng sarcoma (0/30) vs osteosarcoma (38/60) (P<)*
Sarcomas with specific translocations
Sarcomas with
non-specific genetic alterations
Karyotypes
Usually simple
Usually complex
Translocations
Reciprocal & specific, producing fusion genes
Non-reciprocal & non-specific, causing gene copy number changes
Telomere maintenance mechanisms
Telomerase common,
ALT mechanism rare
ALT mechanism more common than telomerase
P53 pathway alterations
Relatively rare, but strong prognostic impact*
More frequent, but limited or no prognostic impact
Incidence in P53-mutant or knockout mice
Not observed
Common
Incidence in bilateral retinoblastoma and
Li-Fraumeni syndrome
Rare
Common
Global gene expression profiles
Robust clustering
Looser clustering
Molecular pathology of sarcomas: two major classes
* Hopkins study: AJP 2004
Evidence of “alternative lengthening of telomeres” (ALT) telomere maintenance mechanism:
Translocation sarcomas (0/9) vs other sarcomas (7/9) (P=)*
Sarcomas with specific translocations
Sarcomas with
non-specific genetic alterations
Karyotypes
Usually simple
Usually complex
Translocations
Reciprocal & specific, producing fusion genes
Non-reciprocal & non-specific, causing gene copy number changes
Telomere maintenance mechanisms
Telomerase common,
ALT mechanism rare
ALT mechanism more common than telomerase
P53 pathway alterations
Relatively rare, but strong prognostic impact
More frequent, but limited or no prognostic impact
Incidence in P53-mutant or knockout mice
Not observed
Common
Incidence in bilateral retinoblastoma and
Li-Fraumeni syndrome
Rare
Common
Global gene expression profiles
Robust clustering
Looser clustering
Molecular pathology of sarcomas: two major classes
* MSKCC study: JCO in press
0
20
40
60
80
100
120






 P5