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Karyopherin Alpha 2 Is an Adverse Prognostic Factor in Clear-Cell and Papillary Renal-Cell Carcinoma
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Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
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Overbeek Kasper A. Cahen Djuna L. Kamps Anne Konings Ingrid C. A. W. Harinck Femme Kuenen Marianne A. Koerkamp Bas Groot Besselink Marc G. van Eijck Casper H. Wagner Anja Ausems Margreet G. E. van der Vlugt Manon Fockens Paul Vleggaar Frank P. Poley Jan-Werner van Hooft Jeanin E. Bleiker Eveline M. A. Bruno Marco J. 《Familial cancer》2020,19(3):247-258
Familial Cancer - In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our... 相似文献
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Iris Cervenka Marie Al Rahmoun Yahya Mahamat-Saleh Agnès Fournier Marie-Christine Boutron-Ruault Gianluca Severi Saverio Caini Domenico Palli Reza Ghiasvand Marit B. Veierod Edoardo Botteri Anne Tjønneland Anja Olsen Renée T. Fortner Rudolf Kaaks Matthias B. Schulze Salvatore Panico Antonia Trichopoulou Clio Dessinioti Katerina Niforou Sabina Sieri Rosario Tumino Carlotta Sacerdote Bas Bueno-de-Mesquita Torkjel M. Sandanger Sandra Colorado-Yohar Maria J. Sánchez Leire Gil Majuelo Leila Lujan-Barroso Eva Ardanaz Susana Merino Karolin Isaksson Salma Butt Ingrid Ljuslinder Malin Jansson Ruth C. Travis Kay-Tee Khaw Elisabete Weiderpass Laure Dossus Sabina Rinaldi Marina Kvaskoff 《International journal of cancer. Journal international du cancer》2020,146(12):3267-3280
Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations. 相似文献
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Lukas Wisgrill Anja Weinhandl Lukas Unterasinger Gabriele Amann Rudolf Oehler Martin L. Metzelder Angelika Berger Thomas M. Benkoe 《Journal of pediatric surgery》2019,54(3):449-454