Diagnosis of gist

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, mostly characterized by activating mutations in one of two genes that code for related tyrosine kinases, namely KIT (75-80%) and PDGFRA (5-10%). Mesenchyme-derived cells of the gastrointestinal tract, such as smooth muscle cells (SMCs), demonstrate high plasticity, a quality often associated with high neoplastic risk. Because tumor progression has often been associated with the re-expression of markers of immature tissue, developmental studies have proven to be a reliable source for the identification of new tumoral markers. Thus, genes involved in the development and plasticity of SMCs demonstrate abnormal expression in GISTs. Using a microarray approach, the inventor identified LIX1 as highly expressed at the earliest stages of stomach development. In chicken, LIX1 was first shown to be expressed in the anterior and posterior intestinal portals, the early buds that will invaginate to give rise to the primary intestinal tube. Moreover, the insect homolog of LIX1, is implicated in the Hippo pathway, which has been at the center of many studies regarding the regulation of the balance between cell proliferation and differentiation. Thus, the present invention relates to the diagnosis of GISTs, using LIX1 as a biomarker. In the present invention, the inventors investigate LIX1 function during digestive smooth muscle development. The inventors show that LIX1 is a novel marker of stomach mesenchymal progenitors and that its expression is strong and highly dynamic. The inventors show that LIX1 positively regulates cell proliferation and SMC determination. Finally, the inventors show that LIX1 is expressed in GISTs and that high LIX1 expression is associated with poor patient prognosis. Scientific publication(s): BMC Biol., 2016 Apr 28, McKey J. et al., LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors, doi: 10.1186/s12915-016-0257-2

Keywords: Cancer, Colorectal Cancer, GIST, Gastrointestinal Stromal Tumors, RT-PCR, Transcriptomics
Patent Application number: EP16 305 159.2
Inventors:
Sandrine FAUREPascal DE SANTA BARBARA
Publications:
BMC Biol. 2016 Apr 28;14:34. doi: 10.1186/s12915-016-0257-2.

Reference:

BIO13315-D1

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Sylvestre CHEA
Sylvestre CHEA
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Patent filling date: 2016-02-11

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