HRAS G13R

Bone sarcomas associated with infarcts exhibit genomic instability, with pronounced copy number variations, especially in Chromosome 12. CDKN2A/B homozygous deletion is highly prevalent, whereas TP53 alterations appear less frequent than in osteosarcomas. MDM2 amplification and H3.3-G34 mutations are recurrent (33%).

Melanotic pigment in the thyroid is practically synonymous with chronic minocycline therapy and rare cases of melanotic medullary thyroid carcinoma...The unusual histology and hitherto unreported molecular findings make this case of primary thyroid melanocytic neoplasm worth reporting. Abstruse origin of melanoma cells in the thyroid gland with molecular signature suggestive of MTC in our case raises a nomenclature and management conundrum, prompting us to revisit the "ontogeny recapitulates phylogeny" theory.

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.

‘RASless’ (KRASlox/HRASKO/NRASKO) mouse embryonic fibroblasts (MEFs) were obtained that in the presence of 600nM tamoxifen (4OHT) resulted in a KRAS knock-out...Combined treatment of HRASG13R/PTEN MEFs with the PIK3CB-specific inhibitor AZD8186 and tipifarnib sensitized cells in non-4OHT (IC50- 100nM:100nM Tipifarnib:AZD8186) and 4OHT (IC50- 100nM:10nM Tipifarnib:AZD8186) conditions... Co-altered mutations of MAPK, PI3K or RTK effectors are found more commonly in HRAS than in KRAS or NRAS-mutant cancers. Co-alteration of PTEN preferentially associated with HRAS-mutations in NSCLC. Deletion of PTEN resulted in resistance to FTI targeted therapy in vitro.

Irrespective of the driving mutation, SSVs in RET occured in high frequency in MTC. The identification of RET SSVs in MTC might represent a novel diagnostic feature for this tumor and may represent an opportunity for better understanding its pathogenesis. Additional work is needed to explore any potential options for targeted therapy for MTC with RET SSVs.

The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.

We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets.

Oral tipifarnib resulted in manageable safety profile and encouraging antitumor efficacy against treatment-refractory UC containing HRAS mutations.

Although Collins et al suggest an age-dependent improvement in mineral abnormalities, we reported two women without OM recovery probably because of extensive bone dysplasia. These cases also reinforce association of CSHS with neoplasms, including first descriptions of patients with rhabdomyosarcoma and giant cell tumor of jaw and the longest follow-ups described until.