CAG repeat size in Huntingtin alleles is associated with cancer prognosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09

AUTHORS

Morgane Sonia Thion, Sophie Tézenas du Montcel, Jean-Louis Golmard, Sophie Vacher, Laure Barjhoux, Valérie Sornin, Cécile Cazeneuve, Ivan Bièche, Olga Sinilnikova, Dominique Stoppa-Lyonnet, Alexandra Durr, Sandrine Humbert

ABSTRACT

The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature. In carriers of BRCA2 mutations, the length of the HTT CAG tract was correlated with lower incidence of ovarian cancer. Among carriers of BRCA1 mutations who developed a breast cancer, its onset occurred 2.4 years earlier in individuals with intermediate HTT alleles (≥27) than in those with a CAG tract <27. Finally, in patients with sporadic HER2 breast cancer, metastasis increased by a factor of 11.10 per 10 additional CAG repeats in HTT. We concluded that whereas long CAG length could be associated with lower cancer incidence, it could also be paradoxically associated with cancer severity (age of apparition and metastasis development). More... »

PAGES

ejhg201613

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ejhg.2016.13

DOI

http://dx.doi.org/10.1038/ejhg.2016.13

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048076557

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26980106


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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318 University of Grenoble Alpes, Grenoble Institut des Neurosciences, INSERM U1216, Grenoble, France
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