My note on paper: Analysis of somatic microsatellite indels identifies driver events in human tumors
Paper: Analysis of somatic microsatellite indels identifies driver events in human tumors
(doi: 10.1038/nbt.3966)
Again, I only note for the gene that I have been interested.
Microsatellites;
*variable-lengths repeats of short DNA motif (usually 1-6 repeat)
*exhibit of high rate of mutation, esp, indel
Gap:
*the relationship of somatic MS indels to cancer is unk, bc of the technical limitation
What they do:
Present two tools
MSMUTect - accurate detection of somatic MS indels
MSMutSig - identification of genes containing MS indels
Apply the tool to whole-exome from
-6747 human tumors; 20 tumors
-identified new >1000 MS indels in cancer genes
-be able to distinguish microsatellite -stable from microstellite instability
-identified 7 MS indel hotspots:
*ACVR2A, RNF43,JAK1,MSH3 (previously known cancer genes -- meaning support the tumor growth)
*ESRP1,PRDM2 and DOCK3
---
MS;
*repetitive short sequences (1-6 bp)
*abundant in non-transcribed region
*can be found in exon and non-translated region
*germ-lines; rate of indel is higher than the single nucleotide substitutions
*the mutation rate depends upon the slippage of DNA pol during replication
---
Tumors with MSI;
*higher numbers of MS indels
*most common in (see figure below)
**colon adenocarcinoma
**stomach adenocarcinoma
**uterine corpus endometrial carcinoma
---
Gap;
*no data support on MS indels related to cancer
*limitation of techniques -- read0length limit and PCR error
*using proper stat to fix
Finding:
1.uncover unique properties of MS indel
2.identified MS loci -- cancer driver
The picture depicts the distribution of indel mutation in each cancer type. The red line represents the average of indel fraction of the mutated loci. (6747 tumors; 20 tumor types)
Results:
1.All seven genes mutated MS indel causes frameshift mutation in exon
2.If frameshift occur near 3'end of gene, non-sense mediated less occur
3. MS indel of RNF43 occur widely from second to last exon, and not correlated with lower expression of RNF43
RNF43
MS indel p.G656fs
1. 40% of MSI colon tumors (16/40)
2. 35% of MSI stomach tumor (24/69)
3. 23% of MSI endometrial (36/155)
RNF43
small percentage of germline MS indel mutation (5/6747, 0.074%) -- raise possibility of inherited pathogenic MS indel
To get more precise result on the relationship between MS indel mutation and cancer, new long-read sequencing is required
(doi: 10.1038/nbt.3966)
Again, I only note for the gene that I have been interested.
Microsatellites;
*variable-lengths repeats of short DNA motif (usually 1-6 repeat)
*exhibit of high rate of mutation, esp, indel
Gap:
*the relationship of somatic MS indels to cancer is unk, bc of the technical limitation
What they do:
Present two tools
MSMUTect - accurate detection of somatic MS indels
MSMutSig - identification of genes containing MS indels
Apply the tool to whole-exome from
-6747 human tumors; 20 tumors
-identified new >1000 MS indels in cancer genes
-be able to distinguish microsatellite -stable from microstellite instability
-identified 7 MS indel hotspots:
*ACVR2A, RNF43,JAK1,MSH3 (previously known cancer genes -- meaning support the tumor growth)
*ESRP1,PRDM2 and DOCK3
---
MS;
*repetitive short sequences (1-6 bp)
*abundant in non-transcribed region
*can be found in exon and non-translated region
*germ-lines; rate of indel is higher than the single nucleotide substitutions
*the mutation rate depends upon the slippage of DNA pol during replication
---
Tumors with MSI;
*higher numbers of MS indels
*most common in (see figure below)
**colon adenocarcinoma
**stomach adenocarcinoma
**uterine corpus endometrial carcinoma
---
Gap;
*no data support on MS indels related to cancer
*limitation of techniques -- read0length limit and PCR error
*using proper stat to fix
Finding:
1.uncover unique properties of MS indel
2.identified MS loci -- cancer driver
The picture depicts the distribution of indel mutation in each cancer type. The red line represents the average of indel fraction of the mutated loci. (6747 tumors; 20 tumor types)
Results:
1.All seven genes mutated MS indel causes frameshift mutation in exon
2.If frameshift occur near 3'end of gene, non-sense mediated less occur
3. MS indel of RNF43 occur widely from second to last exon, and not correlated with lower expression of RNF43
RNF43
MS indel p.G656fs
1. 40% of MSI colon tumors (16/40)
2. 35% of MSI stomach tumor (24/69)
3. 23% of MSI endometrial (36/155)
RNF43
small percentage of germline MS indel mutation (5/6747, 0.074%) -- raise possibility of inherited pathogenic MS indel
To get more precise result on the relationship between MS indel mutation and cancer, new long-read sequencing is required
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