Melan-OMICS: whole-exome and transcriptome sequencing to dissect molecular complexity of cutaneous malignant melanoma
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Data di Pubblicazione:
2014
Citazione:
Melan-OMICS: whole-exome and transcriptome sequencing to dissect molecular complexity of cutaneous malignant melanoma / I. Cifola, A. Pietrelli, M. Severgnini, A. Magi, L. Tattini, E. Mangano, A. Santosh, V. Russo, C. Battaglia, G. De Bellis. ((Intervento presentato al convegno European Society of Human Genetics Conference tenutosi a Milano nel 2014.
Abstract:
Cutaneous melanoma is the most fatal skin cancer and, although some effective
molecular therapies exist, novel targets and drugs are still needed. To
provide new insights for novel targets discovery, we performed an extensive
characterization by next-generation sequencing (NGS) of a collection of
melanoma cell lines derived from metastatic cases. Samples were profiled
by whole-exome sequencing (WES) and RNA-sequencing using Illumina
technology. Starting from WES data, we developed a bioinformatics pipeline
to catalogue 2,172 novel mutations affecting genes in melanoma key
pathways targeted by current therapies (MAPK and glutamate pathways) as
well as genes never described for melanoma [Cifola, 2013]. Moreover, WES
data were used to perform copy number alteration (CNA) analysis using a
novel software developed by us, called Excavator, which is very sensitive and
precise in DNA copies estimation even in situations of great sample heterogeneity
[Magi, 2013]. CNA results were concordant with 250K SNP Array
data and used to explore CN state of mutated genes. To collect and share these
results, we created a Melanoma Exome Database (https://155.253.6.64/
MExDB/). On the same samples, we also carried out RNA-sequencing and
performed both a traditional gene expression analysis and more sophisticated
structural evaluations. Focusing on fusion transcripts, we identified
72 putative events generated by either inter-chromosomal translocations
or intra-chromosomal rearrangements, recently defined “conjoined genes”
and representing an additional gene regulation mechanism. Globally, NGS
proved to be extremely powerful to dissect cancer complexity at both genomic
and transcriptomic levels, and to identify novel potential targets for
personalized treatment of cutaneous melanoma.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
exome sequencing; melanoma; bionformatics; RNA sequencing
Elenco autori:
I. Cifola, A. Pietrelli, M. Severgnini, A. Magi, L. Tattini, E. Mangano, A. Santosh, V. Russo, C. Battaglia, G. De Bellis
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