HRAS Q61R

FNA rinses are a suitable source to perform molecular analysis after morphological evaluation maximizing diagnostic efficiency. Additionally, BRAF V600E is not the sole pathogenic alteration in thyroid cancer, so expanding tests to include other molecular alterations may enhance diagnostic utility using this available material.

This observation reveals a binding site that can potentially be exploited for development of inhibitors against mutant NRAS. Furthermore, the well-resolved catalytic site of this GTPase bound to native GTP provides insight into the stalled GTP hydrolysis observed for NRAS-Q61K.

No recurrence or carcinoma development was observed in any of the IUP cases during the follow-up period. Thus, we confirmed the importance of RAS pathway activation in IUP pathogenesis, an association between RAS family gene mutations and IUP subtypes, and the spread patterns of IUP cells within the surface.

We found that all 23 CAAs showed diffuse and strong membranous RAS Q61R immunoreactivity (100% sensitivity), while none of the 8 OSCCs showed immunoreactivity (100% specificity). The data supports the use of RAS Q61R-specific rabbit monoclonal antibody for diagnostic IHC confirmation of CAA and ruling out OSCC in dogs.

Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.

In conclusion, our study revealed that secondary tumors arising from NS harbor known RAS hotspot mutations and additional genomic alterations, including putative driver mutations and PTCH1 copy-loss. These results could help to define the high-risk group for tumor development in patients with NS and provide evidence for prophylactic resection.

XA improved risk stratification and identification of malignant thyroid disease with a very high ROM in GSC “suspicious” nodules. Although a negative XA result was associated with lower RoM in our cohort, a negative XA result should not be used as a “rule-out” test.

In this post-2017 WHO classification cohort of 554 consecutive PTCs, BRAF V600E mutation is highly prevalent in 87% of the cases. RAS mutations account for only 1.1% of the cases and half of them are classified as encapsulated follicular variant of PTC. Kinase gene fusions are identified in 8.5% of the cases and are clinically relevant given the emerging targeted kinase inhibitor therapy.

Afirma XA detected abnormalities in approximately one-third of Afirma GSC suspicious nodules, of which RAS mutations were the most common finding (68%). Two-thirds of cases labeled suspicious by Afirma GSC did not reveal gene mutations or fusions by Afirma XA testing, suggesting other unknown genetic alterations requiring further investigation.

HRAS mutation, a well-known genetic alteration of low-grade tumor in bladder cancer, was detected only in the high-grade UTUC in the public data, suggesting a rather distinct molecular alteration of UTUC. Also, HRAS alteration was clonally retained in not only the low-grade but also the high-grade components, and was significantly correlated to intratumoral heterogeneity. Our findings can help understand the underlying biology of NI-UTUC cases with HRAS alteration and intratumoral heterogeneity.