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Genome-wide mutation analysis in precancerous lesions of endometrial carcinoma.
Li, Lihong; Yue, Pinli; Song, Qianqian; Yen, Ting-Tai; Asaka, Shiho; Wang, Tian-Li; Beavis, Anna L; Fader, Amanda N; Jiao, Yuchen; Yuan, Guangwen; Shih, Ie-Ming; Song, Yan.
Afiliação
  • Li L; Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
  • Yue P; Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Song Q; State Key Lab of Molecular Oncology, Laboratory of Cell and Molecular Biology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
  • Yen TT; State Key Lab of Molecular Oncology, Laboratory of Cell and Molecular Biology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
  • Asaka S; Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Wang TL; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Beavis AL; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Fader AN; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Jiao Y; Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Yuan G; Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Shih IM; State Key Lab of Molecular Oncology, Laboratory of Cell and Molecular Biology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
  • Song Y; Department of Gynecology Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
J Pathol ; 253(1): 119-128, 2021 01.
Article em En | MEDLINE | ID: mdl-33016334
Clinicopathological evidence supports endometrial atypical hyperplasia (AH) or endometrial intraepithelial neoplasia as the precursor of uterine endometrioid carcinoma (EC), the most common gynecologic malignancy. However, the pathogenic progression from AH to EC remains unclear. Here, we employed whole-exome sequencing to identify somatic mutations and copy number changes in micro-dissected lesions from 30 pairs of newly diagnosed AH and EC. We found that all but one pair of AHs shared the same DNA mismatch repair status as their corresponding ECs. The percentage of common mutations between AH lesions and corresponding ECs varied significantly, ranging from 0.1% to 82%. Microsatellite stable AHs had fewer cancer driver mutations than ECs (5 versus 7, p = 0.017), but among microsatellite unstable AHs and ECs there was no difference in mutational numbers (36 versus 38, p = 0.65). As compared to AH specimens, 19 (79%) of 24 microsatellite stable EC tumors gained new cancer driver mutations, most of which involved PTEN, ARID1A, PIK3CA, CTNNB1, or CHD4. Our results suggest that some AH lesions are the immediate precursor of ECs, and progression depends on acquisition of additional cancer driver mutations. However, a complex clonal relationship between AH and EC can also be appreciated, as in some cases both lesions diverge very early or arise independently, thus co-developing with distinct genetic trajectories. Our genome-wide profile of mutations in AH and EC shines new light on the molecular landscape of tumor progression. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Biomarcadores Tumorais / Transformação Celular Neoplásica / Neoplasias do Endométrio / Carcinoma Endometrioide / Sequenciamento do Exoma / Mutação Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Middle aged País/Região como assunto: America do norte / Asia Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Biomarcadores Tumorais / Transformação Celular Neoplásica / Neoplasias do Endométrio / Carcinoma Endometrioide / Sequenciamento do Exoma / Mutação Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Middle aged País/Região como assunto: America do norte / Asia Idioma: En Ano de publicação: 2021 Tipo de documento: Article