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Semin Cell Dev Biol 64:18–25, Bhawal UK, Tsukinoki K, Sasahira T, Sato F, Mori Y, Muto N, Sugiyama M, Kuniyasu H (2007) Methylation and intratumoural heterogeneity of 14-3-3 sigma in oral cancer. Clin Transl Oncol 16(11):937–941, Gahete MD, Cordoba-Chacon J, Hergueta-Redondo M, Martinez-Fuentes AJ, Kineman RD, Moreno-Bueno G, Luque RM, Castano JP (2011) A novel human ghrelin variant (In1-ghrelin) and ghrelin-O-acyltransferase are overexpressed in breast cancer: potential pathophysiological relevance. J Clin Oncol 36(15_suppl):1009–1009, Tabernero J, Lenz HJ, Siena S, Sobrero A, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C et al (2015) Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Nat Rev Cancer 12(5):323–334, PubMed 865-338-3474 Raymund Zundel. Camillo: The first I was in LA and in the Millennium Dance Complex, I was a 17 years old teenager. Cancer 124(21):4168–4180, Dong N, Shi L, Wang DC, Chen C, Wang X (2017) Role of epigenetics in lung cancer heterogeneity and clinical implication. J Clin Invest 128(4):1371–1383, Hoadley KA, Siegel MB, Kanchi KL, Miller CA, Ding L, Zhao W, He X, Parker JS, Wendl MC, Fulton RS et al (2016) Tumor evolution in two patients with basal-like breast cancer: a retrospective genomics study of multiple metastases. Acta Neuropathol 129(6):849–865, De Mattos-Arruda L, Caldas C (2015) Cell-free circulating tumour DNA as a liquid biopsy in breast cancer. 4:32. 720-543-7026 Celestyna Guilliams. Google Scholar, Abe H, Kawahara A, Azuma K, Taira T, Takase Y, Fukumitsu C, Murata K, Yamaguchi T, Akiba J, Ishii H et al (2015) Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: a comparative study between small biopsy and excision samples. CAS Clin Cancer Res 13(1):81–89, Tabassum DP, Polyak K (2015) Tumorigenesis: it takes a village. Most carcinomas, sarcomas, and astrocytomas display extensive intratumoral morphological variability that, if not taken into account, can lead to an inaccurate or even incorrect diagnosis. Nat Rev Clin Oncol 15(2):81–94, Andor N, Graham TA, Jansen M, Xia LC, Aktipis CA, Petritsch C, Ji HP, Maley CC (2016) Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Although “single hit pathways” are reported, disruptions of several pathways are necessary for a cell to become malignant. hypoxia or lack of nutrients through various pathways) are common to most human tumors (especially in advanced stages) [56]. Clin Cancer Res 21(2):249–257, Zhou M, Li J, Cheng L, Egevad L, Deng FM, Kunju LP, Magi-Galluzzi C, Melamed J, Mehra R, Mendrinos S et al (2015) Diagnosis of “poorly formed glands” Gleason pattern 4 prostatic adenocarcinoma on needle biopsy: an interobserver reproducibility study among urologic pathologists with recommendations. It is increasingly clear that understanding alterations within tumor cells is only part of the picture, and we need to understand interactions between tumors and their microenvironment to account for multiple aspects of tumor progression and therapeutic resilience [55, 98,99,100]. 978-288-3989 Sarine Mabile. 720-543-0232 Nicodemo Altomare. We both couldn‘t sleep so we started to create a choreography out of boredom. The concept of clonal cooperation is based on a single clone being unable to acquire all the necessary properties to be an invasive tumor, such that various clones must act synergistically and complementarily to acquire the characteristics described by Hanahan and Weinberg [49] and the proposed biochemical changes in 10 or more cellular biochemical pathways. Science 355(6330):1103. J Clin Oncol 28(16):2784–2795, PubMed Genet Epigenet 7:19–32, Castellana B, Aasen T, Moreno-Bueno G, Dunn SE, Ramon y Cajal S (2015) Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells. It is a blessing to make people smile with something that makes you happy as well. Every effort should be made to form multidisciplinary teams involving radiologists, nuclear medicine specialists, pathologists, oncologists, systems biologists, molecular biologists, and data scientists. Neoplastic lesions are diagnosed primarily based on pathological examination, both gross and microscopic, but the information obtained may not always be conclusive for a diagnosis of malignancy. Alterations in the expression and activity of specific translation factors and their inhibition by cellular stress conditions (e.g. World J Gastroenterol 12(37):5932–5940, Diaz-Cano SJ (2008) General morphological and biological features of neoplasms: integration of molecular findings. Chromosomal translocations such as those including the ALK gene are demonstrated in anaplastic lymphoma, lung adenocarcinoma, and myofibroblastic tumors [36], and the translocation EWSR1-CREB1 in tumors as different as clear cell sarcoma and angiomatoid fibrous histiocytoma [37]. Lancet Oncol 16(8):937–948, Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y, de Stanchina E, Massague J (2016) Metastatic latency and immune evasion through autocrine inhibition of WNT. Consequently, research is slow, and financial and human resources are not optimized. Did we expect it? Histopathology 53(1):1–19, Yang Q, Yang Y, Zhou N, Tang K, Lau WB, Lau B, Wang W, Xu L, Yang Z, Huang S et al (2018) Epigenetics in ovarian cancer: premise, properties, and perspectives. volume 98, pages161–177(2020)Cite this article. J Clin Pathol 68(9):758–762, Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhsng CZ, Wala J, Mermel CH et al (2013) Pan-cancer patterns of somatic copy number alteration. J Mol Diagn 14(4):376–384, Ramon YCS, Segura MF, Hummer S (2019) Interplay between ncRNAs and cellular communication: a proposal for understanding cell-specific signaling pathways. Gene Ther 5(2):286–287, Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Int J Cancer 60(2):235–243, Sanchez-Prieto R, Quintanilla M, Cano A, Leonart ML, Martin P, Anaya A, Ramon y Cajal S (1996) Carcinoma cell lines become sensitive to DNA-damaging agents by the expression of the adenovirus E1A gene. The tumor clone markers include those involved in the tumorigenic expansion (proliferation) and invasion, the two leading forces driving progression. 865-338-8354 Hoshee Phaup. This variability means that many patients undergo specific therapeutic regimens in situations where perhaps only 10% of the studied tumor cells are positive for the corresponding target. 709-648-2163 Bassianus Herczeg. Front Oncol 5:54, Karachaliou N, Mayo-delas Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, Garcia-Gomez R, Massuti B, Sanchez JM, Porta R et al (2015) Association of EGFR L858R mutation in circulating free DNA with survival in the EURTAC trial. This heterogeneity responds to specific gene expression profiles, thus pointing to the existence of other determinants of intratumor morphological heterogeneity and highlighting the importance of context. This intratumoral differentiation is often patchy, and not well defined in molecular terms. 865-338-3299 Innocenzyo Shifflet . CAS Very suitable for stage performances as a tour or a background dancer. Ann Oncol 25(10):1959–1965, Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Trends Cancer 5(1):1–5, Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic. J Pathol 241(3):375–391, Trinh A, Trumpi K, De Sousa EMF, Wang X, de Jong JH, Fessler E, Kuppen PJ, Reimers MS, Swets M, Koopman M et al (2017) Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry. One important aspect is how representative biopsies reflects the overall tumor histology and biology. Researchers from the National Research Tomsk State University [25] have shown that the morphological heterogeneity in invasive micropapillary carcinoma (IMPC) of the breast is not related to the presence of specific chromosomal aberrations. BMC Cancer 19(1):666, Keith B, Johnson RS, Simon MC (2011) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Watch Queue Queue. I am never going forget this! Part of Springer Nature. 720-543-9412 Wilhemine Hrabovsky. After previous studies by Dotto and Weinberg [91], who observed that normal fibroblasts could inhibit the growth of RAS-transformed keratinocytes in athymic mice, we observed that coinjection of normal fibroblasts together with RAS-transformed keratinocytes induced benign or low-grade malignant squamous lesions with extensive areas of keratinization that were observable by morphology, by immunohistochemistry, and by electron microscopy [90]. However, recent evidence suggests that a tumor is heterogeneous in almost every discernible phenotypic trait as the result of not only genetic influences but also non-genetic sources of variability [2]. Camillo: The first I was in LA and in the Millennium Dance Complex, I was a 17 years old teenager. Camillo: You have to be flexible. Sie werden von Violetta Kromer und Camillo Lauricella trainiert. https://doi.org/10.1111/his.13828, Ramon YCS, Castellvi J, Hummer S, Peg V, Pelletier J, Sonenberg N (2018) Beyond molecular tumor heterogeneity: protein synthesis takes control. NPJ Precis Oncol 1(1):22, Horning SJ (2017) A new cancer ecosystem. Did this video probably jumpstart your career? This collection allowed us to characterize the mutational and copy number aberration (CNA) landscapes across the individual metastasis, to infer the clonal ancestries of metastases, to assess the TME in each individual metastasis, to characterize the predicted neo-antigens, and to assess the TCR repertoires across metastases, providing an unprecedented molecular characterization of lethal breast cancers that had been subjected to multiple lines of systemic therapies [119]. As a final reflection, we firmly believe that research strategies should be optimized. This heterogeneity poses a problem when trying to standardize a therapy in a specific tumor type, requiring a personalized approach based on the particular genetic alterations of the tumor, to improve the response rates to the treatment. Front Genet 10:281, Argani P, Fritsch M, Kadkol SS, Schuster A, Beckwith JB, Perlman EJ (2000) Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. Willkommen auf der offiziellen Support-Page der "S'n'C Kidz". This video is unavailable. Furthermore, some of the most common molecular alterations have been associated with tumors whose morphological characteristics are strikingly distinct. Never. However, the most clinically advanced approach is ctDNA from plasma which closely matches the gene profile of tumor tissue biopsies. Tumor heterogeneity has presented a considerable challenge to matching patients with the right treatment at the right time; therefore, it poses a challenge to accomplish the goals of precision medicine [8, 9]. Enter the last 4 digits above. Even in tumors with constitutive genetic activation of EGFR and HER2, the underlying pathways are not permanently and homogeneously active in all cells [79,80,81,82,83]. Cancer Discov 6(3):286–299, Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang CZ, Shalek AK, Satija R et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. CA Cancer J Clin 66(1):75–88, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM (2013) The cancer genome atlas pan-cancer analysis project. potentially from both primary and various metastatic sites. 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We must establish more rational and ambitious organizational models and strategies, with real networks and professional, well-trained teams. 978-288-9581 Landice Uhlmann. Clin Chem 61(3):514–522, Wang Y, Springer S, Zhang M, McMahon KW, Kinde I, Dobbyn L, Ptak J, Brem H, Chaichana K, Gallia GL et al (2015) Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord. While procuring multiple metastatic tumor samples for genomic studies through NGS and development of patient-derived xenografts or organoids, mechanistic insights gained from research autopsy studies of cancer patients can help identify new targets for therapeutic intervention [114].