Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

Suleiman H. Suleiman, Mahmoud E. Koko, Wafaa H. Nasir, Ommnyiah Elfateh, Ubai K. Elgizouli, Mohammed O E Abdallah, Khalid O. Alfarouk, Ayman Hussain, Shima Faisal, Fathelrahamn M A Ibrahim, Maurizio Romano, Ali Sultan, Lawrence Banks, Melanie Newport, Francesco Baralle, Ahmed M. Elhassan, Hiba S. Mohamed, Muntaser E. Ibrahim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

Original languageEnglish
Article number288
JournalFrontiers in Genetics
Volume6
Issue numberSEP
DOIs
Publication statusPublished - 2015

Fingerprint

Exome
Colorectal Neoplasms
Mutation
Neoplasms
RNA Editing
Hereditary Nonpolyposis Colorectal Neoplasms
Oncogenic Viruses
Insertional Mutagenesis
Pedigree
Mutagenesis
Genes
Carcinogenesis
Nucleotides
Phenotype

Keywords

  • Colorectal cancer
  • ELAVL1/HuR
  • Exome sequencing
  • Network analysis
  • NFkB
  • Pathway analysis

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

Suleiman, S. H., Koko, M. E., Nasir, W. H., Elfateh, O., Elgizouli, U. K., Abdallah, M. O. E., ... Ibrahim, M. E. (2015). Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways. Frontiers in Genetics, 6(SEP), [288]. https://doi.org/10.3389/fgene.2015.00288

Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways. / Suleiman, Suleiman H.; Koko, Mahmoud E.; Nasir, Wafaa H.; Elfateh, Ommnyiah; Elgizouli, Ubai K.; Abdallah, Mohammed O E; Alfarouk, Khalid O.; Hussain, Ayman; Faisal, Shima; Ibrahim, Fathelrahamn M A; Romano, Maurizio; Sultan, Ali; Banks, Lawrence; Newport, Melanie; Baralle, Francesco; Elhassan, Ahmed M.; Mohamed, Hiba S.; Ibrahim, Muntaser E.

In: Frontiers in Genetics, Vol. 6, No. SEP, 288, 2015.

Research output: Contribution to journalArticle

Suleiman, SH, Koko, ME, Nasir, WH, Elfateh, O, Elgizouli, UK, Abdallah, MOE, Alfarouk, KO, Hussain, A, Faisal, S, Ibrahim, FMA, Romano, M, Sultan, A, Banks, L, Newport, M, Baralle, F, Elhassan, AM, Mohamed, HS & Ibrahim, ME 2015, 'Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways', Frontiers in Genetics, vol. 6, no. SEP, 288. https://doi.org/10.3389/fgene.2015.00288
Suleiman, Suleiman H. ; Koko, Mahmoud E. ; Nasir, Wafaa H. ; Elfateh, Ommnyiah ; Elgizouli, Ubai K. ; Abdallah, Mohammed O E ; Alfarouk, Khalid O. ; Hussain, Ayman ; Faisal, Shima ; Ibrahim, Fathelrahamn M A ; Romano, Maurizio ; Sultan, Ali ; Banks, Lawrence ; Newport, Melanie ; Baralle, Francesco ; Elhassan, Ahmed M. ; Mohamed, Hiba S. ; Ibrahim, Muntaser E. / Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways. In: Frontiers in Genetics. 2015 ; Vol. 6, No. SEP.
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AU - Nasir, Wafaa H.

AU - Elfateh, Ommnyiah

AU - Elgizouli, Ubai K.

AU - Abdallah, Mohammed O E

AU - Alfarouk, Khalid O.

AU - Hussain, Ayman

AU - Faisal, Shima

AU - Ibrahim, Fathelrahamn M A

AU - Romano, Maurizio

AU - Sultan, Ali

AU - Banks, Lawrence

AU - Newport, Melanie

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