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According to the company, the 17 fusions include ALK, AXL, BRAF, CCND1, FGFR1, FGFR2, FGFR3, MET, NGR1, NTRK1, NTRK2, NTRK3, PPARG, RAF1, RET, ROS1 as well as THADA.
The patient developed resistance to the drug later in the course of the disease due to the NTRK3 G623R mutation.
Esta enfermedad se puede generar por herencia genetica o por radiacion, y se ven afectados genes como: RET, BRAF, RAS, EIF1AX, PPM1D y CHEK2 y translocaciones que afectan PPARg, NTRK1, NTRK3, THADA y FGFR2, ademas de alteraciones moleculares como cadherina epitelial, molecula neural de adhesion celular (N-CAM), p-catenina, p53 y p63 [1,3].
El CPT presenta mutaciones patogenas bien caracterizadas, incluidas mutaciones en BRAF, RAS, EIF1AX, PPM1D y CHEK2 y translocaciones que afectan BRAF, PPARg, NTRK1, NTRK3, THADA y FGFR2 .
Ignyta and the European Organisation for Research and Treatment of Cancer (EORTC) declared that they will partner through EORTCs Screening Patients for Efficient Clinical Trial Access (SPECTA) biomarker screening move to recognize patients who harbor a gene rearrangement to NTRK1, NTRK3, ROS1 or ALK and therefore may be competent for Ignytas global STARTRK-2 Phase 2 clinical study.
In the cooperation between SPECTA and Ignyta, eligible patients showing positive for a gene rearrangement to NTRK1, NTRK3, ROS1 or ALK are to be specially suggested for enrollment in the STARTRK-2 clinical trial.
24) NTRK3 fusions have been reported in papillary thyroid carcinomas.
48) The most common translocation partner with ETV6 is NTRK3 because of a t(12;15)(p13;q25) translocation; however, rare tumors have been found to show ETV6 rearrangement involving another, as yet unknown, gene (ie, ETV6-X), and these cases may have more aggressive behavior.
The recurrent balanced chromosomal translocation t(12,15)(p13; q25), which results in the fusion of the ETV6 gene on 12p13, a transcriptional regulator, with the NTRK3 gene on 15q25, a membrane receptor kinase, (5) is so far specific to MASC among other salivary gland tumors.
81) The most common mutations in papillary thyroid cancer (PTC) are point mutations of the BRAF and RAS genes and rearrangements of RET/PTC, NTRK1, and NTRK3 (a recent discovery), all of which are able to activate the mitogen-activated protein kinase (MAPK) pathway.
On the other hand, the NTRK3 gene is located on chromosome 15 and encodes a membrane receptor tyrosine kinase.
Similar to the namesake tumor in the breast, the salivary gland mammary analogue secretory carcinoma harbors a translocation between the ETV6 and the NTRK3 genes.
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