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HGSOC mutational processes are established early and are patient-specific.
HGSOC mutational processes are established early and are patient-specific. A, Representative p53 IHC and hematoxylin and eosin images of the hypothetical progression series of HGSOC in a patient with STIC, and invasive lesions in the fallopian tube, ovary, and abdominal omentum. B, Laser capture microdissection of the tumor compartment from omentum. C, Workflow to elucidate the spatiotemporal pattern of genomic alterations in HGSOC to capture tumor phylogenies and core events. D, Frequencies of SNV by anatomic site and patient reveal that mutational burden is patient-specific rather than determined by anatomic tumor location. Average mutational burden across the patient cohort is approximately 1 somatic mutation per megabase (50 mutations total per tumor sample). E, Identification of an age-related mutational signature class characterized by high rates of C>T substitutions in all samples of the patient cohort reveals a comparable mutational process underlying disease progression in all patients examined. FT, invasive fallopian tube tumor; Ov, invasive ovarian tumor; Om, omental metastasis. Mark A. Eckert et al. Cancer Discov 2016;6: ©2016 by American Association for Cancer Research
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