This was confirmed in a landmark study by Wiesner et al (169) in 2014, which demonstrated in-frame fusion transcripts resulting in the overexpression of kinase genes (including ROS1, ALK, NTRK1
, RET, and BRAF) in just more than 50% of spitzoid neoplasms.
For example, a mouse model of AEL that included mutations in TP53 and NTRK1
, a kinase in a signaling pathway, was exquisitely sensitive to the inhibitor larotrectinib.
Prognostic significance of RET and NTRK1
rearrangements in sporadic papillary thyroid carcinoma.
According to the company, the Seraseq NTRK FFPE RNA reference material contains 15 clinically significant NTRK RNA fusions across NTRK1
, NTRK2 and NTRK3 genes and are to be used by clinical laboratories looking to validate their detection by next-generation sequencing (NGS) methods.
We found significant differences in six: NGF (p < 0.001), NGFR (p < 0.05), NTRK1
(p < 0.01), GFRA1 (p < 0.01), GFAP (p < 0.001), and GDNF (p < 0.05) (see Figure 2).
The other diagnoses were excluded after the genetic study which detected mutations in the NTRK1
gene responsible for CIPA in 2015.
ThyroSeq v2 panel Gene mutations Gene fusions Gene expression (RNA) (DNA) (RNA) BRAF RET RET PGK1 Pan-cell NRAS TSHR PPARG KRT7 HRAS AKT1 NTRK1
TG Thyroid cell KRAS TP53 NTRK3 TTF1 PIK3CA GNAS BRAF NIS PTEN CTNNB1 ALK Calcitonin MTC TERT EIF1AX PTH Parathyroid KRT20 Metastatic
Montano, "Phosphorylation of NTRK1
at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: a potential novel prognostic marker for breast cancer," Modern Pathology, vol.
En la segunda fase, con las 27 proteinas extraidas (NTRK1
, ELAVL1, RAB5A, GTSE1, OCRL, NXF1, GRB2, CLTC, RAB8A, RAB1A, RAB6A, SSX2IP, XPO1, FAM109A, FAM109B, SPINT2, GOLGA5, CEP128, SCLT1, CEP170, HERC2, SCN2B, ENPP6, VSIG4, BTN2A1, CACNG4, RAB14), se construyo una red de interaccion en el Software Cytoscape version 3.3.0 (Shannon, et al., 2003).
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].
In this condition genetic mutation occurs at NTRK1
gene which is inherited as autosomal recessive disorder.
Such efforts have already resulted in the identification of fusions for FGFR1, FGFR2, and FGFR3 (33,34) as well as for ROS1, (35,36) RET, (36) and NTRK1
, (37) with clinical trials also having been initiated with corresponding inhibitors.