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19406207capr140257-sup-136129_1_supp_2640725_nbkksg.pdf (85 kB)

Supplemental Table 5 from Notch1 Mutations Are Drivers of Oral Tumorigenesis

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posted on 2023-04-03, 19:46 authored by Evgeny Izumchenko, Kai Sun, Sian Jones, Mariana Brait, Nishant Agrawal, Wayne Koch, Christine L. McCord, David R. Riley, Samuel V. Angiuoli, Victor E. Velculescu, Wei-Wen Jiang, David Sidransky

Supplemental Table 5. List of 108 primer pairs designed by Fluidigm Assay Design Group and used in this study for NOTCH1 amplification. Table summarizes the GC-content, length distribution and location of the Access Array amplicons.

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ARTICLE ABSTRACT

Disruption of NOTCH1 signaling was recently discovered in head and neck cancer. This study aims to evaluate NOTCH1 alterations in the progression of oral squamous cell carcinoma (OSCC) and compare the occurrence of these mutations in Chinese and Caucasian populations. We used a high-throughput PCR-based enrichment technology and next-generation sequencing (NGS) to sequence NOTCH1 in 144 samples collected in China. Forty-nine samples were normal oral mucosa from patients undergoing oral surgery, 45 were oral leukoplakia biopsies, and 50 were chemoradiation-naïve OSCC samples with 22 paired-normal tissues from the adjacent unaffected areas. NOTCH1 mutations were found in 54% of primary OSCC and 60% of premalignant lesions. Importantly, almost 60% of patients with leukoplakia with mutated NOTCH1 carried mutations that were also identified in OSCC, indicating an important role of these clonal events in the progression of early neoplasms. We then compared all known NOTCH1 mutations identified in Chinese patients with OSCC with those reported in Caucasians to date. Although we found obvious overlaps in critical regulatory NOTCH1 domains alterations and identified specific mutations shared by both groups, possible gain-of-function mutations were predominantly seen in Chinese population. Our findings demonstrate that premalignant lesions display NOTCH1 mutations at an early stage and are thus bona fide drivers of OSCC progression. Moreover, our results reveal that NOTCH1 promotes distinct tumorigenic mechanisms in patients from different ethnical populations. Cancer Prev Res; 8(4); 277–86. ©2014 AACR.See related perspectives, p. 259 and p. 262

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