Molecular characterization of families without identified genetic cause hereditary colon cancer

12 06 2014

During the last decades, a great effort has been made to elucidate the genetic de de familial colorectal cancer cases. In spite of that, including the latest technological advances that have allowed to study genome and exome full de de affected families members, It is not yet possible to explain large part de genetic predisposition to colorectal cancer.

Program de Cancer hereditary del ICO-IDIBELL line de work directing the researcher Laura Velasco Valley is dedicated to the study of molecular de families de high risk which is not yet known genetic cause de this predisposition to develop cancer de colon and rectum.


In order to identify new genes de Cáncer hereditario has been sequenced the full exome, i.e. the coding part del genoma, de de cancer de one de these families affected members. The family studied showed a pattern de apparently dominant inheritance, and family members with cancer had not developed polyps in the colon. Unexpectedly, identified mutations in a gene already known de predisposition to colorectal cancer and polyposis colon that follows a recessive pattern de legacy, Gene MUTYH.

Based on the results obtained in this study, proposed a reorientation process de selection de families for the study del de MUTYH which provides the presence de a pattern de dominant inheritance because of the risk that hold a single allele mutations, the possibility de there are no polyps at the time del diagnosis, as well as de that there are tumors with molecular traits de other de hereditary colorectal cancer syndromes such as de microsatellite instability.

On the other hand, supporting studies, de a specific mutation analysis [KRAS c.34G>T (p.G12C)], characteristic de tumors associated to MUTYH, test de selection de eligible families for the study del gene in germ line.

In addition to involvement del program de Cáncer Hereditario this study has had the collaboration de de de Frankfurt University groups (Dr. Guido Plötz), de Universidad de Oviedo (DrDrXosé S. Bridge) and del Centro Nacional de Genomic analysis (CNAG).


Another study team de Valle del to characterize families with no known genetic cause hereditary colorectal cancer, It has conducted a comprehensive study de molecular traits de developed tumors in the context del hereditary colorectal cancer non-polyposis without alterations in genes de del DNA repair, that it would cause the syndrome de Lynch.

To do this, Genomic alterations have been studied, mutations in genes relevant to cancer de colon as they are KRAS, BRAF, TP53 and PIK3CA, and the level de global methylation de both hereditary tumors as sporadic CpG Islands. The results obtained indicate that these hereditary tumors show genomic profiles very similar to profiles de sporadic tumors, both suggestive de high chromosomal instability and low-level de de CpG Islands methylation.

However, they have identified some specific features, as del chromosome gain 2, the loss de 10q or a lower frequency de mutations in TP53, It could be relevant for the clinical management de these patients or for identification de causing defects in germ line de aggregation de cancer in these families. For this project de hereditary Cancer program has had the collaboration de other groups del IDIBELL-ICO (Unit de biomarkers and susceptibility and Laboratorio de Investigación translational).


References de items

Nuria Seguí, Matilde Navarro, Marta Pineda, Nicole Koger, Fernando Bellido, Sara González, Olga Campos, Silvia Iglesias, Rafael Valdés-Mas, Adriana López-Dóriga, Marta Gut, Ignacio Blanco, Conxi Lazarus, Gabriel Capellá, Xosé S. Bridge, *Guido Plötz, *Laura Valle. Exome sequencing identifies MUTYH mutations in a family with colorectal cancer and an atypical phenotype. Gut 2014 [Epub ahead of print]


Fernando Bellido, Marta Pineda, Rebeca Sanz-Pamplona, Matilde Navarro, Marga Nadal, Conxi Lazarus, Ignacio Blanco, Victor Moreno, Gabriel Capellá, Laura Valle. Comprehensive molecular characterisation of hereditary non-polyposis colorectal tumours with mismatch repair proficiency. European Journal of Cancer 2014 [Epub ahead of print]
 [en línea] Barcelona (ESP):, 12 de junio de 2014 [REF. 03 in June of 2014] Available on Internet:



Leave a comment

You can use these tags : <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>