Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B −/−:89A3B +/−:27A3B +/+), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.

Background: The nucleolar MSP58 protein is a candidate oncogene implicated in cellular transformation.Results: MSP58 is associated with BRG1 and induces cellular senescence through the p53/p21 pathway.Conclusion: MSP58 has both tumor-suppressing and -promoting functions.Significance: This work reveals a novel role for MSP58 in cellular senescence and suggests that MSP58 may have further prognostic and therapeutic implications.

A 13-year-old spayed female Labrador Retriever was presented with severe progressive tetraparesis. The neuroanatomic localization was the C1-C5 spinal cord segments with brainstem or cranial nerve involvement. Magnetic resonance imaging revealed diffuse T1weighted and T2-weighted hyperintense lesions with strong contrast enhancement spreading through meninges of the cervical spinal cord and the brain. Few small round areas showing T1weighted hyperintensity and T2-weighted hypointensity were scattered within the lesions. Cerebrospinal fluid analysis revealed neoplastic round cells and possible melanocytes. Malignant melanoma was suspected. At necropsy, the brain and the entire spinal cord were covered with thick, dark membranous tissue. Based on histopathologic findings, a positive response against Melan-A, and no melanoma identified outside the central nervous system, primary meningeal melanomatosis was diagnosed.

Oral cavity squamous cell carcinoma (OSCC) is a destructive disease with its increasing new cases annually. OSCC is usually diagnosed at advanced clinical stage which leads to the poor outcomes of patients. Currently, no biomarkers provide capability for sufficient early detection of OSCC. Cancer-associated auto-antibody (auto-Ab) holds potentials as promising biomarkers for cancer detection because auto-Ab is easily detected with well-established secondary reagents. To ameliorate the detection of OSCC, we evaluated the capability of auto-Ab to 9 proteins as the OSCC biomarkers with multiplexed bead-based immunoassay, as the salivary levels of the 9 proteins are elevated in OSCC patients. The multiplexed bead-based assay has been established to simultaneously detect the salivary levels of the 9 auto-Abs and anti-p53, a well-characterized OSCC biomarker. Compared to the healthy individuals, the salivary levels for 8 of 9 auto-Abs as well as anti-p53 were significantly elevated in OSCC patients. The salivary levels of the 7 of 9 auto-Abs were significantly increased in individuals with oral potentially malignant disorder compared to the control group. In addition, the salivary levels of 8 of 9 auto-Abs as well as anti-p53 were statistically significant in early-stage OSCC patients. Moreover, the marker panel of the 9 auto-Abs can improve the detection of OSCC. Collectively, we have established the platform for detection of maker panels and the salivary auto-Abs are potential biomarkers for OSCC screening. Citation Format: Pei Chun Hsueh, Chih Ching Wu. Salivary auto-antibodies as diagnostic markers of oral cavity squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1148.