AGK-BRAF fusion

No abstract available

This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

No abstract available

Although the methodology is still evolving, our findings suggest that this non‐invasive approach can be incorporated into the routine management of patients with malignant thyroid neoplasm as it may help the early detection of therapeutically targetable mutations. We emphasize that liquid biopsy test can be repeated through the follow‐up to complement existing tests with low cost and convenience for the patient. We also anticipate that that this blood test may help early detection of thyroid tumors.

Previous therapy with pembrolizumab provided a best response of stable disease (SD) after 11 weeks of therapy...Patient 2 is a 35-year-old white male with a TRIM33-BRAF fusion malignant melanoma, and progressed after treatment with radiation, nivolumab, and nivolumab + ipilimumab... Early results from the first three patients of this ongoing trial showed tovorafenib is generally well tolerated and has encouraging antitumor activity in BRAF-fusion melanoma.

Analysis of two tissue microarrays comprised of 130 tumor cores from multiple tissue sites of the first 10 NSCLC RTD donors revealed that 66% of tumor cores had >1% LAG3 expression in CD3+ T cells. Among the three patients with ALK fusion-positive NSCLC, 83% (5 of 6 cores), 85% (6 of 7 cores), and 100% (18 of 18 cores) of the tissue cores had >1% LAG3 expression in T cells. The median LAG3 expression in T cells measured by mIF was 1.8% in 99 tumor cores from the ALK fusion-negative study cohort versus 7.3% in the 31 cores from the ALK fusion-positive subset (p=0.004).

These patients received various therapies including pembrolizumab, nivolumab, capmatinib, bevacizumab, osimertinib, brigatinib, erlotinib, and alectinib, as well as sotorasib. Collection and sequencing of RTD samples provides an opportunity to detect resistance mutations and to understand more about post-treatment disease progression and tumor heterogeneity. The identification of drivers by comprehensive NGS tissue testing in two cases serves as a reminder about the value of such testing when no drivers are identified by small panels or blood-based NGS testing.

We found that CCV is primarily a BRAF-driven tumor, with most also harboring secondary oncogenic mutations and multiple chromosomal gains and losses. Moreover, our findings suggest that molecular analysis could potentially help risk stratify CCV.

Moreover, can also observe a trend to a more disrupted chromatin organization in AGK-BRAF tumors and tumors from <10 y.o. patients, which can be associated with the aggressiveness of the disease in these cases. Further analysis are needed to better understand wether AGK-BRAF fusion is associated with poor prognosis in pediatric PTC and if it could be related to a high genomic instability caused by this fusion.

The 3D nuclear telomere signature was able to detect differences in telomere architecture in tumours, compared to normal. Further analysis is necessary to define whether nuclear telomere architecture and specific genetic alterations observed in pediatric thyroid cancer are associated.