SMC1A (Structural Maintenance Of Chromosomes 1A)

We see recurrent somatic mutations in MCMs particularly at a novel mutational hotspot in SMC3, consistent with a neoplastic process. Mutations in cohesin complex genes are associated with disease recurrence.

The sequential acquisition of cooperating genetic lesions supports clonal evolution and highlights the need for molecular monitoring and novel therapeutic strategies. The authors have confirmed clinical trial registration is not needed for this submission.

P1, N=13, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jan 2027 | Trial primary completion date: Dec 2025 --> Apr 2025

Furthermore, we observed differential effects of Rad21 and Smc3 deletion on leukemia development and secondary engraftment despite only minor differences in gene expression. These results demonstrate that cohesin mutations are not only tolerated in Cbfb::MYH11-expressing cells, they likely do not confer a strong selective advantage and are therefore not preferentially selected for during clonal evolution of this leukemia.

These findings indicate that γT3 and δT3 inhibit HCC2998 cell proliferation by activating the DDR pathway, highlighting their potential as therapeutic agents to overcome cell cycle arrest resistance in CRC. This study provides critical insights into the molecular actions of γT3 and δT3, supporting their further investigation as promising candidates for CRC intervention.

We further validate the RNA-associating abilities of chromatin-conformation regulators SMC1A, SMC3 and RAD21, as well as the metabolic enzyme PHGDH. PRIM-seq enables systematic discovery and prioritization of RNA-binding proteins and their targets without gene- or protein-specific reagents.

Moreover, silencing SMC1A effectively inhibits lung cancer cell invasion, migration, and G1/S phase transition, while promoting apoptosis. These findings indicate that SMC1A has the potential to be a new therapeutic target for CoLCNEC treatment.

TRPS1 is highly expressed in PTSS and has certain diagnostic values. The diagnosis of PTSS also requires combination of patient's medical history with thorough imaging studies.

The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

Cohesin mutations are typically heterozygous and result in haploinsufficiency and/or loss-of-function, and although they might be expected to cause defects in chromosome segregation, the sister chromatid cohesion function of the complex is unlikely the driving mechanism of tumorigenesis, given the lack of aneuploidy in cohesin-mutant cancers. In this review, we will focus on the prevalence of somatic mutations in cohesin subunits across different cancer types, the influence of these mutations on chromatin organization and gene regulation, the resulting cellular and disease phenotypes, and the therapeutic potential of targeting the mutant cohesin complex.

Approximately 40% of breast cancer tissue exhibited cytoplasmic/membranous localization of p-SMC1A, whereas nuclear expression was observed in normal breast tissues. Moreover, elevated phosphorylation levels were significantly associated with higher tumor grade and metastasis.

P1, N=12, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025