NRAS mutation

P1/2, N=54, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P1/2, N=5, Completed, National Cancer Institute (NCI) | N=70 --> 5 | Recruiting --> Completed

Unexpectedly, lipodystrophic mice did not show T cell expansion, were protected from colitis, and displayed a defect in the development of proinflammatory T cells, which could be reversed by allogeneic fat transplantations, indicating that clonal T cell expansion in AGLCD is not primarily caused by lipodystrophy. Instead, gene sequencing revealed a T cell-intrinsic de novo neuroblastoma RAS viral oncogene homolog (NRAS) mutation, implicating somatic mosaicism as a facilitator of clonal T cell expansion and intestinal inflammation in AGLCD.

c-KIT mutations resulted in 35% of the children tested. The RT-PCR technique resulted more sensitive in finding c-KIT D816V, while NGS in detecting other mutations whose prognostic roles require further investigation.

Digital PCR enabled the ultra-low detection of Variant Allele Frequencies (VAFs), identifying high molecular burdens (e.g., P05, VAF 49%) correlating with rapid decline, and capturing early molecular residue in P04 (VAF 0.62%). Our preliminary findings confirm that personalized longitudinal VAF tracking via digital PCR provides superior prognostic value, serving as a robust tool for recurrence monitoring in personalized CRC therapy.

P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Feb 2027

Our findings suggest significant clinical, pathologic, and molecular correlations in an Australian cohort of advanced melanoma treated with ICIs. Patients with NF1 mutation exhibited higher TMB, which was associated with improved response to ICIs.

Histopathological features overlapped among all adenoma types, and no single feature was lesion-specific. Applying quantitative thresholds may improve diagnostic accuracy and reduce interobserver variability.

PTPN11 mutations were also associated with decreased overall survival (HR 1.36, 95% CI 1.01-1.85, P = 0.046) compared to individuals without the mutation.ConclusionMutations in the RAS pathway, particularly NRAS, KRAS, and PTPN11, are associated with inferior survival outcomes in adult patients with MDS. These findings underscore the prognostic relevance of RAS mutations and highlight their potential utility in refining current risk stratification models such as IPSS-M, WPSS, and MDAS.

Co-occurring genetic alterations with RAS mutations markedly increased the risk of malignancy compared with isolated RAS mutations (Fisher's exact test, two-tailed p = 0.0026) and were associated with more aggressive tumor phenotypes, whereas isolated RAS mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

SIADs occur in a substantial subset of CMML patients and are associated with significantly better LFS and reduced risk of leukaemic transformation, with a trend towards improved OS.