br Our study has several limitations This is a
Our study has several limitations. This is a retrospective analysis of publicly available data. The sequencing depth of the primary and metastatic samples was on average 77× , thus we cannot rule out that subclonal mutations were missed. In addition, we could per-form mutational signature analysis separately only in the subset of the matched primary and metastatic ECs with sufficient shared and private mutations. More comprehensive analyses including whole-genome sequencing may better define the mutational processes that are driving the progression from primary to metastatic disease in EC.
Despite these limitations, our study demonstrated that EC is a het-erogeneous disease with multiple mutational processes shaping the mutational spectra of these lesions. Although the molecular subtype classification proposed by TCGA for endometrioid and serous carcino-mas captures some of this heterogeneity, our mutational signature anal-ysis identified examples that would result in their reclassification. We also observed a shift from aging- or POLE- to MSI-related mutational processes in the progression from primary to metastatic ECs in a subset of cases. With the decreasing costs of genomic sequencing, routine whole-genome or even multiple-site sequencing of tumors is rapidly becoming reality in the clinical setting. In the era of precision medicine, information on the mutational processes shaping the GW311616 of a given EC may provide important information in addition to the specific muta-tions and gene copy number alteration.
Supplementary data to this article can be found online at https://doi.
Conflict of interest
N. Riaz reports research support from Pfizer and Bristol-Myers Squibb, and personal fees from the Illumina Speakers' Bureau, outside the submitted work. J.S. Reis-Filho reports personal/consultancy fees from VolitionRx, Page.AI and Goldman Sachs, outside the submitted work. The remaining authors have no conflicts of interest to declare.
J.S. Reis-Filho is funded in part by the Breast Cancer Research Foun-dation. Research reported in this publication was supported in part by a Cancer Center Support Grant of the National Institutes of Health/Na-tional Cancer Institute (Grant No. P30CA008748).
We thank S.H. Kim and L.A. Moukarzel for critical reading of the manuscript.
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Journal of Oral Biosciences
Analysis of oral microbiota in Japanese oral cancer patients using 16S rRNA sequencing
Yasuharu Takahashi a, e, 1, Jonguk Park b, 1, Koji Hosomi c, Tomonori Yamada d, Ayaka Kobayashi d, Yuji Yamaguchi d, Susumu Iketani d, Jun Kunisawa c, Kenji Mizuguchi b, Nobuko Maeda e, Tomoko Ohshima e, *
a Department of Oral Microbiology, Doctor of Philosophy in Dental Science, Graduate School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama-shi, Kanagawa, 230-8501, Japan b Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Asagi, Saito, Ibaraki-shi, Osaka, 567-0085, Japan