Schematic representation of the clinical workflow for lung cancer diagnosis, treatment, and follow-up. 563-447-0191 Iriss Detienne. Very suitable for stage performances as a tour or a background dancer. Nat Rev Cancer 15(8):473–483, Solimini NL, Luo J, Elledge SJ (2007) Non-oncogene addiction and the stress phenotype of cancer cells. Moreover, the deep learning tumor prediction heat map can be quite complementary to pathologists’ “workflow.” An algorithm can detect, for example, metastatic carcinoma in lymph nodes, or tumor budding in the colon or cervix, and help to recognize histologic patterns associated with higher malignant grades in gliomas [203], and moreover, can score the degree of malignancy in tumors such a prostate adenocarcinomas where quantification of the histological patterns are underway [197, 198]. Difficulties in obtaining tumor tissue using invasive surgical procedures have led to the development of liquid biopsies for several cancer types [165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184]. Google Scholar, Gomez-Martin C, Concha A, Corominas JM, Garcia-Caballero T, Garcia-Garcia E, Iglesias M, Lopez JA, Ramon y Cajal S, Rojo F, Palacios J et al (2011) Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society of Pathology (SEAP) for HER2 testing in gastric carcinoma. Nat Rev Cancer 12(5):323–334, PubMed  Cancer Cell 28(5):666–676, Pan W, Gu W, Nagpal S, Gephart MH, Quake SR (2015) Brain tumor mutations detected in cerebral spinal fluid. 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. 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. Nat Commun 6:8760, Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE et al (2014) An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Mol Oncol 10(3):464–474, Siravegna G, Marsoni S, Siena S, Bardelli A (2017) Integrating liquid biopsies into the management of cancer. Enter the last 4 digits above. Every tumor is unique as a result of its interactions with the host and the genetic and epigenetic variability. Finally, one of the most powerful techniques is the study of tumor heterogeneity at the cellular level. Nat Rev Cancer 11(8):541–557, Cantile M, Marra L, Franco R, Ascierto P, Liguori G, De Chiara A, Botti G (2013) Molecular detection and targeting of EWSR1 fusion transcripts in soft tissue tumors. Am J Surg Pathol 39(10):1331–1339, Park SY, Gonen M, Kim HJ, Michor F, Polyak K (2010) Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. Nucleic Acids Res 45(W1):W195–W200, Roychowdhury S, Chinnaiyan AM (2016) Translating cancer genomes and transcriptomes for precision oncology. Eur Radiol 26(8):2798–2807, Eberwine J, Sul JY, Bartfai T, Kim J (2014) The promise of single-cell sequencing. In addition, chemotherapy and radiotherapy can trigger selection of resistant clones [2, 109, 110], induce new mutations and other genetic and chromosomal rearrangements [21, 111], recover functionality of previously inactivated genes whose potential had been exploited in synthetic lethal interactions [112], activate cellular dedifferentiation and transdifferentiation programs [97], and even potentiate the development of specific populations by non–cell-autonomous mechanisms [113]. One important aspect is how representative biopsies reflects the overall tumor histology and biology. 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. The identification of factors involved in this interplay between malignant clones, which mediate tumor growth and metastasis, may be one promising approach in the understanding of cancer [101]. Nevertheless, not all oncogenic changes are diagnostic determinants of a specific tumor type or give rise to the emergence of a specific morphologic pattern. TA received support from Instituto de Salud Carlos III (grants PI16/00772 and CPII16/00042), co-financed by the European Regional Development Fund (ERDF). 709-648-9478 Valeska Kidman. State-of-the-art digital image acquisition and quantification algorithms, which integrate biophysical parameters to capture the spatial variation in tumor architectures, are likely to play an essential role in this [16]. It is likely that combinations will be needed for most subtypes. Clin Transl Oncol 13(9):636–651, PubMed  Cancer Biol Ther 8(15):1463–1469, Yoshizawa A, Fukuoka J, Shimizu S, Shilo K, Franks TJ, Hewitt SM, Fujii T, Cordon-Cardo C, Jen J, Travis WD (2010) Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Examples have been published for skin cancer (both melanoma and squamous cell carcinoma), lung adenocarcinoma, glioma, gastric carcinoma, and others [135, 199,200,201,202]. Although “single hit pathways” are reported, disruptions of several pathways are necessary for a cell to become malignant. 978-288-3142 Saulisbury Mattfeld. The same is with dancing, so it doesn‘t matter whether it‘s Locking, Popping, Jazz, contemporary, Salsa or Ballet… you don‘t have to be a pro in every style but an overall basic training leads you to control your body better , find your own style and bring it to perfection. We both couldn‘t sleep so we started to create a choreography out of boredom. J Eur Acad Dermatol Venereol 21(9):1220–1228, Diaz-Cano SJ (2000) Designing a molecular analysis of clonality in tumours. Cancer 107(8):1801–1811, Armengol G, Rojo F, Castellvi J, Iglesias C, Cuatrecasas M, Pons B, Baselga J, Ramon y Cajal S (2007) 4E-binding protein 1: a key molecular “funnel factor” in human cancer with clinical implications. Share. This critical literature review considers how prayer is practiced throughout the course of life, why it is practiced, and the influences upon prayer behaviors throughout different life stages. J Pathol 191(4):343–344, Diaz-Cano SJ (2001) Are PCR artifacts in microdissected samples preventable? Chromosome instability (CIN) and microsatellite instability (MSI) have been described as two alternative pathways to cancer [53, 69, 70]. 2). In fact, there is a huge intertumoral heterogeneity between tumors with the same histology in different individuals. Jamal-Hanjani M, Quezada SA, Larkin J, Swanton C (2015) Translational implications of tumor heterogeneity. 978-288-9581 Landice Uhlmann. N Engl J Med 373(20):1895–1898, Sehgal R, Sheahan K, O’Connell PR, Hanly AM, Martin ST, Winter DC (2014) Lynch syndrome: an updated review. was just incredible and definitely a big boost for both of us. Camillo: What fascinates me the most is the possibility to share my love and passion for dancing with so many people. Nat Genet 47(4):320–329, Zhang S, Jing Y, Zhang M, Zhang Z, Ma P, Peng H, Shi K, Gao WQ, Zhuang G (2015) Stroma-associated master regulators of molecular subtypes predict patient prognosis in ovarian 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. Hello everyone, here is the new video “Turn Up the Music” Choreographed by Camillo Lauricella & Robert Lenart, performed with Yuki Shibuya, and as always we chose the best of the best for our readers. The importance of such approach is highlighted by the observation of clustered populations within a tumor that differ in gene expression [133], as well as genetic composition [134]. 978-288-6197 Jaketah Gladhill. The use of liquid biopsies may pave the way for a more detailed, real-time patient-tracking approach allowing the modification of therapeutic strategies throughout the disease. Sci Rep 5:13248, Werner HM, Mills GB, Ram PT (2014) Cancer systems biology: a peek into the future of patient care? Sci Rep 4:4709, Seol H, Lee HJ, Choi Y, Lee HE, Kim YJ, Kim JH, Kang E, Kim SW, Park SY (2012) Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance. However, unless large numbers of samples are provided for each tumor, this approach can easily fail to identify patches of genetically distinct cells [130,131,132]. What were/are your idols? Don’t forget to share it with your friends if you liked it. Inflammatory cytokines are another example, released by stromal or immune cells, which can alter DNA methylation and other epigenetic markers. 720-543-9839 Zeke Jax. DanceAware: You worked as a choreographer for German TV shows like „Got to Dance“ (Pro7/SAT.1), „Dance Dance Dance“ (RTL) and also for „So You Think You Can Dance“ in Portugal and in the Ukrain. 563-447-5385 Kanti Woolen. In this context, some caution should be taken for the evaluation of early epithelial neoplasms. Nat Med 18(12):1835–1840, Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, Loguidice L, Soto H, Garrett M, Zhu LD et al (2013) BEAMing and droplet digital PCR analysis of mutant IDH1 mRNA in glioma patient serum and cerebrospinal fluid extracellular vesicles. 978-288-5151 Laksha Griese. Deep learning methodology, with the generation of thousands of clinical-pathological diagnostic cases, can promote the development of algorithms based on this methodology that could represent a breakthrough in the pathological diagnosis As an example, Google released TensorFlow, an algorithmic development framework for distributed computing, to the general scientific and technical community. Having more than 1 Mio. Attempts are currently being made to quantify these areas and grade tumors, generally according to the least-differentiated area or the area with the highest degree of cytologic malignancy [17, 18]. Core biopsies often only reflect a spatiotemporal snapshot of the whole tumor and are therefore unlikely to be fully informative about the clonal composition [123,124,125,126,127,128,129]. Tumor heterogeneity is associated with poor prognosis and outcome [3,4,5,6]. J Clin Endocrinol Metab 91(3):1150–1158, Diaz-Cano SJ (2007) Kinetic topographical heterogeneity in follicular thyroid neoplasms and growth patterns. But I look up to every human being that is ambitious about following his own dreams, believes in himself, respect and love others and never forget where he came from. One way to achieve this balance is isolate by microdissection multiple relatively small regions of tumors that more likely represent the balance of morphologically distinct units. Science 355(6330):1103. Genome Res 22(2):271–282, Lobo J, Barros-Silva D, Henrique R, Jeronimo C (2018) The emerging role of Epitranscriptomics in Cancer: focus on urological tumors. Nat Genet 47(3):199–208, Raychaudhuri M, Schuster T, Buchner T, Malinowsky K, Bronger H, Schwarz-Boeger U, Hofler H, Avril S (2012) Intratumoral heterogeneity of microRNA expression in breast cancer. 720-543-0124 Averi … As a little kid you don‘t think a lot, you just do things you like. 865-338-3299 Innocenzyo Shifflet . Cytometry A 91(6):566–573, Heng YJ, Lester SC, Tse GM, Factor RE, Allison KH, Collins LC, Chen YY, Jensen KC, Johnson NB, Jeong JC et al (2017) The molecular basis of breast cancer pathological phenotypes. 709-648-2014 Rowly Pagliuca. Cancer Genet 216-217:37–51, Assenov Y, Brocks D, Gerhauser C (2018) Intratumor heterogeneity in epigenetic patterns. 563-447-1502 Haskel Hergott. Hier findet ihr die aktuellsten News, Dates, Clips & Pics. Given that phenotypes generated by changes in genetic material are the substrate of clonal development and selection and adaptation to the microenvironment for each of these pathways (e.g., insensitivity to apoptosis, self-sufficiency in cell proliferation, acquisition of so-called replicative immortality), several significant genetic changes must occur (Fig. PLoS One 13(9):e0203459, Yu KH, Zhang C, Berry GJ, Altman RB, Re C, Rubin DL, Snyder M (2016) Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features. 978-288-2423 Jefarey … Although some molecular alterations are recurrent in some tumors, not all the tumors of the same type, and similar morphology, show the same genetic profile. Dancing is art and you have to learn how to control your body first. b Cooperation between several clones to invade and metastasize. 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]. DanceAware: What lacks the german dance scene compared to the USA and why? There are 74 results for persons named Jean Witt. Cancer Discov. Tweet. Sci Transl Med 6(224):224ra224, Olsson E, Winter C, George A, Chen Y, Howlin J, Tang MH, Dahlgren M, Schulz R, Grabau D, van Westen D et al (2015) Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. 2 min intadv jazz dance routine to applause dance by lady gaga. 720-543-3992 Volya Romack. In this sense, the first point to underline would be that the presence of different morphological patterns within the same tumor suggests the coexistence of various clones, each subject to specific genetic changes or different environmental pressures that are not necessarily shared by clones present in other areas. Never. Camillo: Why I started? Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Google Scholar, Mroz EA, Rocco JW (2013) MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Nat Biotechnol. - 199.247.9.71. Willkommen auf der offiziellen Support-Page der "S'n'C Kidz". PubMed Central  Did this video probably jumpstart your career? Mol Oncol. This open-source machine learning tool is free for any qualified scientist and is specialized in cognitive computing. Algorithm-related applications for primary diagnosis, intraoperative diagnosis, training, quantification of immunohistochemistry, or diagnostic consultation are likely to progress significantly over the next few years. 563-447-2506 Damicke Storck. These algorithms are likely to help pathologists in reaching a faster, more accurate diagnosis and significantly reduce the pathologist-dependent discordance in histopathological diagnosis. Sci Transl Med 7(283):283ra254, McGranahan N, Swanton C (2017) Clonal heterogeneity and tumor evolution: past, present, and the future. Science 344(6190):1396–1401, Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, Shafi S, Johnson DH, Mitter R, Rosenthal R et al (2017) Tracking the evolution of non-small-cell lung cancer. Proc Natl Acad Sci U S A 112(31):9704–9709, Shi R, Wang PY, Li XY, Chen JX, Li Y, Zhang XZ, Zhang CG, Jiang T, Li WB, Ding W et al (2015) Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients. Morphological and genetic heterogeneity is the result of a multistep process of tumorigenesis that leads to subclonal tumor cell populations with distinct traits, according to current paradigms [2, 5, 8, 21]. Nat Rev Cancer 19(9):495–509, Ramon y Cajal S, Suster S, Halaban R, Filvaroff E, Dotto GP (1991) Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes. Camillo: You have to be flexible. She has a golden cuff on her left arm and an. Proc Natl Acad Sci U S A 99(20):13085–13089, Romo-Bucheli D, Janowczyk A, Gilmore H, Romero E, Madabhushi A (2017) A deep learning based strategy for identifying and associating mitotic activity with gene expression derived risk categories in estrogen receptor positive breast cancers. … To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Correspondence to Sci Rep 8(1):3395, Michaut M, Chin SF, Majewski I, Severson TM, Bismeijer T, de Koning L, Peeters JK, Schouten PC, Rueda OM, Bosma AJ et al (2016) Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Thus, targeted therapies in heterogeneous neoplasms lead to transient tumor regression and subsequent selective outgrowth of existing resistant populations, leading to recurrence in the long run. DanceAware: Do you still have to fight with stage fright and do you remember your first stage performance? Sci Transl Med 2(20):20ra14, Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O'Shaughnessy J, Kinzler KW, Parmigiani G, Vogelstein B et al (2012) Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. https://doi.org/10.1007/s00109-020-01874-2, DOI: https://doi.org/10.1007/s00109-020-01874-2, Over 10 million scientific documents at your fingertips, Not logged in Though I realized much later that I want to make dancing to my profession. I am never going forget this! Mod Pathol 13(1):29–36, Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M (2011) Advances in sarcoma genomics and new therapeutic targets. 709-648-6693 Yancey Kerstiens. What is special about this place? Cancer Discov 5(10):1086–1097, Hong MK, Macintyre G, Wedge DC, Van Loo P, Patel K, Lunke S, Alexandrov LB, Sloggett C, Cmero M, Marass F et al (2015) Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. PLoS One 10(4):e0123352, Gerdes MJ, Sood A, Sevinsky C, Pris AD, Zavodszky MI, Ginty F (2014) Emerging understanding of multiscale tumor heterogeneity. 865-338-9333 Ludovic Magstadt. In many malignant tumors, it is common to find well-differentiated areas adjacent to poorly or moderately differentiated areas. Had to bring my latin roots back! The histopathological diagnosis should integrate molecular analysis (genome sequencing, transcriptome profiling) and protein expression profiling (especially analyses including next-generation sequencing (NGS) techniques) and be able to include gene signatures that are characteristic of a different prognosis or clinical treatment [55, 70, 92, 94, 130, 135,136,137] (Fig. 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. Tumors are composed of mosaics of cancer cells with different characteristics and varying sensitivities to anticancer therapies. J Pathol 225(2):222–231, De Carvalho DD, Sharma S, You JS, Su SF, Taberlay PC, Kelly TK, Yang X, Liang G, Jones PA (2012) DNA methylation screening identifies driver epigenetic events of cancer cell survival. Proc Natl Acad Sci U S A 85(17):6389–6393, Perez-Villamil B, Romera-Lopez A, Hernandez-Prieto S, Lopez-Campos G, Calles A, Lopez-Asenjo JA, Sanz-Ortega J, Fernandez-Perez C, Sastre J, Alfonso R et al (2012) Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior. Otherwise, dissecting tumor heterogeneity involves emerging strategies such as multiregional sequencing, analysis of autopsy samples, single-cell sequencing, and longitudinal analysis of liquid biopsy samples [52]. 4:32. The study of the tumor immune microenvironment appears quite promising and includes treatment with immune checkpoint antibodies, with programmed death 1 (PD-1 and PDL-1) targeted agents, and novel immunotherapies. A summary of main molecular events related with intratumoral heterogeneity is shown in Table 1. Jovannah Lauricella. Nat Commun 7:12474, Djuric U, Zadeh G, Aldape K, Diamandis P (2017) Precision histology: how deep learning is poised to revitalize histomorphology for personalized cancer care. The Millennium Dance Complex is just „the place to be“! These factors, which play a significant role in the control of protein synthesis, could be sensitive tumor targets in a large number of malignant tumors [79, 83, 161, 162]. 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. Sci Transl Med 4(162):162ra154, Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D et al (2012) Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. 978-288-2326 Clean Takeshita. 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. 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. What fascinates you about being on stage? This call appears to originate from City State. Clinical implications of intratumor heterogeneity: challenges and opportunities, https://doi.org/10.1016/j.molonc.2015.12.001, https://doi.org/10.1158/2159-8290.CD-15-1483, https://doi.org/10.1007/s00109-020-01874-2. 709-648-9868 Fantasya Ambriz. For example, in colon adenocarcinomas, a subtype harbors a relevant profile of epigenetic alterations [64]; this is also seen in urological [65] and other tumors [57, 58, 71]. Science 352(6282):169–175, Notta F, Mullighan CG, Wang JC, Poeppl A, Doulatov S, Phillips LA, Ma J, Minden MD, Downing JR, Dick JE (2011) Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Cell 158(5):1110–1122, Cheung KJ, Gabrielson E, Werb Z, Ewald AJ (2013) Collective invasion in breast cancer requires a conserved basal epithelial program. The tumor microenvironment analysis focuses the attention on the qualities that potentiate clonal expansion and invasion of tumor cells. It has been shown that most of the targets considered as druggable and for which Food and Drug Administration (FDA)-approved therapeutics are available are not expressed in a uniform or homogeneous manner in tumor tissue. 709-648-1635 Shakyra Roh. In collaboration with Cambridge CRUK, our group has performed extensive multi-platform profiling of metastases in 10 warm autopsies of patients with lethal multi-therapy-resistant breast cancers (DNA sequencing, RNA sequencing, the T cell receptor (TCR) sequencing, and immunohistochemistry (IHC)) of multiple individual metastases (range 5–36 metastases per case, 182 individual metastases to 22 organ sites). Examples include the variable threshold of positivity for the expression of the HER2 receptor in gastric adenocarcinoma [10], progesterone and estrogen receptors in breast tumors [11], the EML4-ALK translocation in lung adenocarcinoma [12], B-RAF mutations in melanoma, and the 1p/19q allelic loss in oligodendrogliomas [13, 14]. Cell 153(1):38–55, Rastetter M, Schagdarsurengin U, Lahtz C, Fiedler E, Marsch W, Dammann R, Helmbold P (2007) Frequent intra-tumoural heterogeneity of promoter hypermethylation in malignant melanoma. This ranges from mutual beneficial cooperation between cells, which nurture features such as growth and metastasis, to the narrow escape and survival of clonal cell populations that have adapted to thrive under specific conditions such as hypoxia or chemotherapy. Information View; 646-480-4262 (6464804262) - Kobee Minshall - Nwyrcyzn01, New York: More Info → 646-480-8948 (6464808948) - Rudyard Garbin - Nwyrcyzn01, New York Taban Lauricella. A representative example can be seen in signaling in the Ras/MAPK and PTEN/PI3K/AKT axes in lung adenocarcinomas, where specific mutations, amplifications, gene expression, and translocations in membrane receptors, as in other genes downstream, can enable the tumor cell hallmark of uncontrolled proliferation [60, 63]. Artificial intelligence. In fact, it may be affected by the microenvironment and stress situations such as starving or hypoxia [62, 85]. Therefore, we can deduce that genomic and epigenomic diversity are not mutually exclusive but can be explained by a unified evolutionary process, giving rise to more robust evolutionary models than clonal relationships inferred from genetic or epigenetic datasets alone. In Germany, you just don‘t have as many different teachers / choreographers you can learn from on a high level as in the United States. Cancer Res 69(9):3866–3873, Fan S, Ramalingam SS, Kauh J, Xu Z, Khuri FR, Sun SY (2009) Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues. Thus, it is the adoption of both genetic and non-genetic subclonal changes that endows cancer with enough phenotypical plasticity to adapt to microenvironmental pressures and successfully overcome the barriers posed by antitumoral therapy. We have proposed the term tissunomics, whereby a diagnosis is individually assessed based upon a combined picture derived from the clinical, pathological, molecular, and protein expression data of the tumor and its surrounding microenvironment [55]. The tumor takes control of translation by various mechanisms to cover the demands associated with high proliferation rates or to promote translation of specific messengers that are favorable to tumor progression (survival, pro-angiogenic, invasion, and metastasis) (reviewed in [89]). Moreover, local hypoxia may induce the expression of histone demethylases and other epigenetic modifiers that subsequently modulate the expression of genes linked to a specific phenotype (e.g., leading to epithelial to mesenchymal transition). PLoS Med 14(1):e1002222, Mattos-Arruda LD, Sammut S-J, Ross EM, Bashford-Rogers R, Greenstein E, Morganella S, Rueda OM, Martinez-Saez E, Peg V, Cortés J et al (2018) The integrated genomic and immune landscapes of lethal metastatic breast cancer (MBC). Therefore, within what we understand as molecular heterogeneity, regional differences in epigenetic status have been observed in different types of cancer that can act, in much the same way as genetic alterations, as drivers of the tumor process. Several studies, comparing blood and tissue biopsies, have confirmed that this approach has high specificity, although variable sensitivity is reported. The Millennium Dance Complex is just „the place to be“! Ann Oncol 25(9):1729–1735, Rothe F, Laes JF, Lambrechts D, Smeets D, Vincent D, Maetens M, Fumagalli D, Michiels S, Drisis S, Moerman C et al (2014) Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer.