Two isoleucyl tRNAs that decode synonymous codons divergently regulate breast cancer metastatic growth by controlling translation of proliferation-regulating genes.

The human genome contains 61 codons encoding 20 amino acids. Synonymous codons representing a given amino acid are decoded by a set of transfer RNAs (tRNAs) called isoacceptors. We report the surprising observation that two isoacceptor tRNAs that decode synonymous codons become modulated in opposing directions during breast cancer progression. Specifically, tRNAIleUAU became upregulated, whereas tRNAIleGAU became repressed as breast cancer cells attained enhanced metastatic capacity. Functionally, tRNAIleUAU promoted and tRNAIleGAU suppressed metastatic colonization in mouse xenograft models. These tRNAs mediated opposing effects on codon-dependent translation of growth-promoting genes, consistent with genomic enrichment or depletion of their cognate codons in mitotic genes. Our findings uncover a specific isoacceptor tRNA pair that act in opposition, divergently impacting growth-regulating genes and a disease phenotype. Degeneracy of the genetic code can thus be biologically exploited by human cancer cells via tRNA isoacceptor shifts that causally facilitate the transition toward a growth-promoting state.

Identification of occult metastatic disease via lymphoscintigraphy-guided neck dissection in N0 oral squamous cell carcinoma.

BACKGROUND: The purpose of this study is to assess the efficacy of lymphoscintigraphy-guided neck dissection (LSG-ND) in the treatment of N0 oral squamous cell carcinoma. METHODS: A retrospective cohort study of patients with N0 oral squamous cell carcinoma (SCC) who had either LSG-ND or neck dissection (ND) at our institution between 2008 and 2020. RESULTS: Eighty-seven patients met criteria with N0 oral squamous cell carcinoma with no previous treatment or neck surgery (27 LSG-ND, 60 ND). Sentinel lymph nodes were identified on the contralateral side in 14.8% of patients with unilateral tumors in the LSG-ND group, with 22.2% of cases with unexpected lymphatic drainage outside ipsilateral levels I-III. No recurrences to date have occurred in the LSG-ND cohort, while 13.3% of patients with ND had regional recurrence (p = 0.04). CONCLUSIONS: LSG-ND provides a greater ability to identify occult metastatic disease with a significant reduction in regional recurrence in N0 oral SCC.