TEST:

MSK-IMPACT

Our results suggest that MYC-dependency likely depends on many factors including, but not limited to, total copy number of the detected amplification, lineage specific factors, concomitant presence or absence of additional oncogenic alterations, and in some cases amplification focality.

These tumors are highly aggressive with poor prognosis. The limited sample size shows a polarized trend in survival data.

Evaluated as a single platform, TumorOriginPredictor achieved over 72% top-3 accuracy across 12 cancer types and exceeded 80% for prevalent cancers. Clinically validated with 770 real-world profiles and deployed on Azure cloud, it provides real-time predictions, promoting individualized treatment by eliminating empirical therapies, reducing costs and time, and improving survival through a scalable, trustworthy AI platform.

NF1 mutation is the strongest gene-level correlate of lung-selective metastasis in cutaneous melanoma. The NF1-mutant subtype may represent a dual-biomarker population and could warrant both pulmonary surveillance and prospective evaluation for immunotherapy.

In addition, rare germline variant association analysis revealed that germline variation in ASXL1 had the strongest association with lung cancer susceptibility among all solid tumors. Collectively, our findings support a model in which smoking-associated expansion of ASXL1-mutant clones contributes to lung cancer development and suggest that gene-specific CHIP metrics may enhance risk stratification and early detection strategies.

We additionally characterize Uterine Clear Cell Carcinoma as a distinct histologic entity (n = 73; 3.0%) and report the POLE + TP53 co-mutant group (n = 90; 3.8%). These findings refine the molecular classification of EC in clinically meaningful ways: they support class-level immunotherapy eligibility based on dMMR status regardless of the specific MMR gene altered, demonstrate that POLE-ultramutated classification requires variant-level pathogenicity assessment, and identify TP53-mutant/CNH patients as the population with the most urgent unmet therapeutic need.

In this pan-cancer cohort, 71% of RET LP/PV findings were incidental, with no prior personal or family history of MTC. High-risk surveillance and potential thyroidectomy are warranted in patients with an incidental germline RET LP/PV finding due to high rates of precursor lesions and MTC even among these patients.

The cutpoint that maximized difference in OS was four metastases, but incorporating genetic alteration information modified this criterion. These findings were proof of principle that integrating multimodal data beyond number of lesions can better identify patients with metastatic NSCLC who may be candidates for MDT.

A new analysis of tumor data from the MSK-IMPACT dataset revealed that the effects of cancer driver mutations differ based on their context, and that HLA alleles vary considerably by ancestry. Both findings have potential therapeutic implications.

Collectively, genomic alterations detected by clinical NGS panels provide potential new biomarkers for risk stratification that can be integrated with conventional parameters to provide improved prognostication and guide therapeutic strategies.

P2, N=30, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2026 --> Feb 2027

Multivariate analysis confirmed that 1q gain predicts poor outcomes independently of CD8 + T-cell infiltration, B-cell infiltration, tumor mutational burden, and PD-L1 status. These findings establish chromosome 1q gain as a compelling biomarker of immunotherapy resistance in melanoma and highlight aneuploidies as underappreciated drivers of immune evasion in this disease.