Thursday, January 31, 2013

NOMENCLATURE OF GENES IN SARCOMA  (TO BE FURTHER DEVELOPED)

1.ALT REPAIR GENE:  British researcher have suggested that this gene of Mesenchymal origin
is one of the 2 mechanism of control of cell mortality at Telomere level.  At this level, life of the cell which is linked to length of the Telomere tail can by activation of Telomere which release the ALT network of genes which in turn stop immortality.  Mesenchymal Cancers to keep living will desactivate this process by Mutation here.  Opening up a target therapy option.
 This Alternative lengthening of Telomere function is related to and work in conjunction with repair mechanisms at Nuclear DNA (ERCC-1, which impart susceptibility to Cisplatin), at transcription gene level (CSA, CSB) and at the level of the double strand DNA (ATM, Ku80, PKC, BRCA, RAD 50).  We should stress the inter-relation between Telomerase activity with both the failure of DNA repair which lead to aging, and the proliferative inputs from NSUN5 and MYEOF (Myeloma)... DSC54 and WNT54 are related gene.
British investigator suggest these changes to be seen in MFH, Liposarcoma, GBM, Osteosarcoma, and Ewing sarcoma.   We should stress the inter-relation between Histone and Telomerase activation which is mostly repressive of negative,  Mutation of in the histone is needed to unveil Telomerate amplification.   

2. P53 
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At least half of the Sarcoma will show activity at P53, the cellular Molecule of the year in 1993,
in up to 10% of cases, the P53 will actually be mutated. It is either overexpressed or suppressed in the rest of the cases of Sarcoma.  The P53 is suppressed if repression occur at P14 or at CDKN2A or if MDM2 is overexpressed.  P14 shield P53 from the effect of MDM2.  P53 is also over expressed if its degradation is stopped at the proteasome.

At nuclear level, Acetylated P53 combines to P300 and promote P21 and Puma leading to Apoptosis.  This effect can be blocked by Fusion protein  EWS-Fli1 in Ewing Sarcoma, and by upregulation of Histone DE-Acelase 1 which effectively block down transcription effect of P53.

if you count right, there are 6 potential target of interaction with P53, if you include upstream toward the membranes...calling for Multitarget therapy in those condition where wild type P53 is overexpressed!

GENE PROFILING IS A MUST STEP IN CANCER TREATMENT!

MDM2
KRAS
BRAF
ETV3
EAT2
TGFBR
CDKN2A
FLI 1
ERG
EWSR
MIC   (CD99)
EA1F
PI3K
(LY29004)
EWS-ATF
MAP KINASE
KIT
PDGFR
PAX3-FKHR
EWS
TLS-CHOP
TAF2N
FACTOR 1 PROMOTER
ERB-2
HSP
PPAR
CDK
EGFR
PTEN
P21
RB
TELOMERE--LACK OF TRF-2
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BASAL CELL
CK 5
CK 15
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NG2 BRAIN NEUROGLIA 2

CHECK 185 DEL aG-1
6174DEL IT-2
5382 InS C
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REGULATOR OF CELL CYCLE
CDK, CCNB, CENPE, AURORA KB, PLK1

ALSO CHECK MAD2,POLE2,CDC2,TOPK,GMNN
GPS,
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BREAST CANCER
KI-67
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 EGFR IN MESOTHELIOMA
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WE ARE WORKING HARD AT CRBCM
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