oncogenomics explorer2

Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com

OncoGenomics Explorer Taming Big Data

22 March 2012


Which are the most frequently mutated genes in ovarian serous carcinoma?

Samples from ovarian serous

carcinoma


TP53, BRCA1 and BRCA2 are the three most frequently mutated genes

TP53 is mutated in almost all tumors


Mutation of the p53 gene is the key event in the development of high-grade tumors.

Unlike low-grade serous carcinoma, mutations of KRAS, BRAF, or ERBB2 occur very infrequently in

high-grade carcinoma.


Most high-grade tumors are characterized by TP53 mutations and lack mutations of KRAS,

BRAF, or ERBB2.Vang R., et al., 2009: Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems.


Serous ovarian cancer is also characterized by a low prevalence but statistically recurrent

mutations in a number of other genes, including NF1, RB1 and FAT3.


Study for example the proportions of point mutations or AA types in NF1...


...or study the mutations in NF1 in detail with the Gene viewer

Can be zoomed all the way down to sequence level

- The blue boxes represent the exons - Substitutions are shown as red vertical lines, insertions as light blue triangles, and deletions as pink triangles

- The SIFT score predicts whether a mutations will affect protein function


Is there a correlation between copy number variations of CCNE1 and overall survival of

the patients ?

Select the gene/genes of interest, in this case CCNE1


Overall survival tends to be lower for patients with CCNE1 amplification

The Cancer Genome Atlas Research Network, 2011: Integrated genomic analyses of ovarian carcinoma


RAB25 seems to be epigenetically silenced in a subset of HG-OvCa tumors

The Cancer Genome Atlas Research Network, 2011:

Integrated genomic analyses of ovarian

carcinoma


Genes with correlated CNV and expression include KRAS, POP4 and C19orf2

Wrzeszczynski KO. et al, 2011: Identification of tumor suppressors and

oncogenes from genomic and epigenetic features in ovarian cancer


Are genes in a region of frequent copy number gain differentially expressed between amplified

and unamplified groups of samples?

Define the two groups to be compared, for example samples with copy number gain vs. samples with normal copy number

Select the genes to be included, for example all genes in chromosome region 3q26


A volcano plot presenting the results of expression analyses between amplified and

unamplified samples in the 3q26 region

The results are shown as a volcano plot that enables the identification of genes that display high differences in expression that also are statistically significant


MYNN is a gene that is located in a region of frequent copy number gain on 3q26.2. It is differently expressed

between amplified and unamplified groups

MYNN shows a strong correlation between copy number and expression

Ramakrishna M. et al., 2010: Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis


In the volcano plot, an interesting group of genes can be selected

Select for example genes with significant p-values and large difference estimates


A heat map can be drawn of the genes from the defined gene selection and of the samples from the two selected

sample groups

...and examine a summary of clinical covariates

Select an interesting cluster of samples in the heat map...


Find out how genetic values correlate with clinical reference data...

Study for example how expression values of genes in chromosome region 8p correlate with overall survival


...or how genetic values correlate with genetic reference data

Study for example how expression values of genes in chromosome region 8p correlate with CNVs of BRCA1

Interesting genes can be selected for

further analysis


- Find new drug targets- Find new biomarkers- Stratify patient groups- Find clinical correlations


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