The Landscape of Actionable Gene Fusions in Colorectal Cancer

Filippo Pagani, Giovanni Randon, Vincenzo Guarini, Alessandra Raimondi, Michele Prisciandaro, Riccardo Lobefaro, Maria Di Bartolomeo, Gabriella Sozzi, Filippo de Braud, Patrizia Gasparini, Filippo Pietrantonio, Filippo Pagani, Giovanni Randon, Vincenzo Guarini, Alessandra Raimondi, Michele Prisciandaro, Riccardo Lobefaro, Maria Di Bartolomeo, Gabriella Sozzi, Filippo de Braud, Patrizia Gasparini, Filippo Pietrantonio

Abstract

The treatment scenario of metastatic colorectal cancer (mCRC) has been rapidly enriched with new chemotherapy combinations and biological agents that lead to a remarkable improvement in patients' outcome. Kinase gene fusions account for less than 1% of mCRC overall but are enriched in patients with high microsatellite instability, RAS/BRAF wild-type colorectal cancer. mCRC patients harboring such alterations show a poor prognosis with standard treatments that could be reversed by adopting novel therapeutic strategies. Moving forward to a positive selection of mCRC patients suitable for targeted therapy in the era of personalized medicine, actionable gene fusions, although rare, represent a peculiar opportunity to disrupt a tumor alteration to achieve therapeutic goal. Here we summarize the current knowledge on potentially actionable gene fusions in colorectal cancer available from retrospective experiences and promising preliminary results of new basket trials.

Keywords: biomarker; colorectal cancer; gene fusions; translocation.

Conflict of interest statement

F.P. has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Servier, Lilly, Merck-Serono, Roche. M.D.B. has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Lilly, Servier, Incyte, Celgene. F.d.B. has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Novartis. F.P. (Filippo Pagani), G.R., V.G., A.R., M.P., R.L., G.S., and P.G. declare no conflict of interest.

Figures

Figure 1
Figure 1
Genetic map of BRAF and RET and their partner genes. (A) Genetic and physical map of the chromosome 7, indicating (in the enlarged rectangles) the location of BRAF (in red) and some of its gene partners (in blue). (B) Moreover, for chromosome 10, containing RET (in red), some of the intrachromosomal genes partners are indicated in blue. Maps and gene location are derived from the website of the University of California Santa Cruz Genome Browser (http://genome.ucsc.edu/), with adaptations.

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