Skip to main content

Advertisement

SpringerLink
Log in

Genetics of personalized medicine: cancer and rare diseases

  • Commentary
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

The 21st annual meeting of the Portuguese Society of Human Genetics (SPGH), organized by Luísa Romão, Ana Sousa and Rosário Pinto Leite, was held in Caparica, Portugal, from the 16th to the 18th of November 2017. Having entered an era in which personalized medicine is emerging as a paradigm for disease diagnosis, treatment and prevention, the program of this meeting intended to include lectures by leading national and international scientists presenting exceptional findings on the genetics of personalized medicine. Various topics were discussed, including cancer genetics, transcriptome dynamics and novel therapeutics for cancers and rare disorders that are designed to specifically target molecular alterations in individual patients. Several panel discussions were held to emphasize (ethical) issues associated with personalized medicine, including genetic cancer counseling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. E.T. Wang, R. Sandberg, S. Luo, I. Khrebtukova, L. Zhang, C. Mayr, S.F. Kingsmore, G.P. Schroth, C.B. Burge, Alternative isoform regulation in human tissue transcriptomes. Nature 456, 470–476 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Q. Pan, O. Shai, L.J. Lee, B.J. Frey, B.J. Blencowe, Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40, 1413–1415 (2008)

    Article  PubMed  CAS  Google Scholar 

  3. T. Maniatis, B. Tasic, Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418, 236–243 (2002)

    Article  PubMed  CAS  Google Scholar 

  4. D.L. Bentley, Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr. Opin. Cell Biol. 17, 251–256 (2005)

    Article  PubMed  CAS  Google Scholar 

  5. J.P. Staley, C. Guthrie, Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell 92, 315–326 (1998)

    Article  PubMed  CAS  Google Scholar 

  6. Z. Zhou, L.J. Licklider, S.P. Gygi, R. Reed, Comprehensive proteomic analysis of the human spliceosome. Nature 419, 182–185 (2002)

    Article  PubMed  CAS  Google Scholar 

  7. P.J. da Costa, J. Menezes, L. Romão, The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease. Int. J. Biochem. Cell Biol. 91, 168–175 (2017). https://doi.org/10.1016/j.biocel.2017.07.013

    Article  PubMed  CAS  Google Scholar 

  8. C.J. David, J.L. Manley, Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev. 24, 2343–2364 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. B. Sumithra, U. Saxena, A.B. Das, Alternative splicing within the Wnt signaling pathway: role in cancer development. Cell. Oncol. 39, 1–13 (2016)

    Article  CAS  Google Scholar 

  10. M. Imielinski, A.H. Berger, P.S. Hammerman, B. Hernandez, T.J. Pugh, E. Hodis, J. Cho, J. Suh, M. Capelletti, A. Sivachenko, C. Sougnez, D. Auclair, M.S. Lawrence, P. Stojanov, K. Cibulskis, K. Choi, L. de Waal, T. Sharifnia, A. Brooks, H. Greulich, S. Banerji, T. Zander, D. Seidel, F. Leenders, S. Ansén, C. Ludwig, W. Engel-Riedel, E. Stoelben, J. Wolf, C. Goparju, K. Thompson, W. Winckler, D. Kwiatkowski, B.E. Johnson, P.A. Jänne, V.A. Miller, W. Pao, W.D. Travis, H.I. Pass, S.B. Gabriel, E.S. Lander, R.K. Thomas, L.A. Garraway, G. Getz, M. Meyerson, Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150, 1107–1120 (2012)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. J. Hernández, E. Bechara, D. Schlesinger, J. Delgado, L. Serrano, J. Valcárcel, Tumor suppressor properties of the splicing regulatory factor RBM10. RNA Biol. 13, 466–472 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  12. E.G. Bechara, E. Sebestyén, I. Bernardis, E. Eyras, J. Valcárcel, RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation. Mol. Cell 52, 720–733 (2013)

    Article  PubMed  CAS  Google Scholar 

  13. L. Wurth, P. Papasaikas, D. Olmeda, N. Bley, G.T. Calvo, S. Guerrero, D. Cerezo-Wallis, J. Martinez-Useros, M. García-Fernández, S. Hüttelmaier, M.S. Soengas, F. Gebauer, UNR/CSDE1 drives a post-transcriptional program to promote melanoma invasion and metastasis. Cancer Cell 30, 694–707 (2016)

    Article  PubMed  CAS  Google Scholar 

  14. A.R. Morris, N. Mukherjee, J.D. Keene, Systematic analysis of posttranscriptional gene expression. Wiley Interdiscip. Rev. Syst. Biol. Med. 2, 162–180 (2010)

    Article  PubMed  CAS  Google Scholar 

  15. L. Wurth, F. Gebauer, RNA-binding proteins, multifaceted translational regulators in cancer. Biochim. Biophys. Acta-Gene Regul. Mech. 1849, 881–886 (2015)

    Article  CAS  Google Scholar 

  16. P. Papasaikas, J.R. Tejedor, L. Vigevani, J. Valcárcel, Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery. Mol. Cell 57, 7–22 (2015)

    Article  PubMed  CAS  Google Scholar 

  17. A.K. Goroncy, S. Koshiba, N. Tochio, T. Tomizawa, M. Inoue, S. Watanabe, T. Harada, A. Tanaka, O. Ohara, T. Kigawa, S. Yokoyama, The NMR solution structures of the five constituent cold-shock domains (CSD) of the human UNR (upstream of N-ras) protein. J. Struct. Funct. Genom. 11, 181–188 (2010)

    Article  CAS  Google Scholar 

  18. G. Triqueneaux, M. Velten, P. Franzon, F. Dautry, H. Jacquemin-Sablon, RNA binding specificity of Unr, a protein with five cold shock domains. Nucleic Acids Res. 27, 1926–1934 (1999)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. D. Huang, H. Pospiech, T. Kesti, J.E. Syva, Structural organization and splice variants of the POLE1 gene encoding the catalytic subunit of human DNA polymerase ε. Biochem. J. 339, 657–665 (1999)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. C. Palles, J.B. Cazier, K.M. Howarth, E. Domingo, A.M. Jones, P. Broderick, Z. Kemp, S.L. Spain, E.G. Almeida, I. Salguero, A. Sherborne, D. Chubb, L.G. Carvajal-Carmona, Y. Ma, K. Kaur, S. Dobbins, E. Barclay, M. Gorman, L. Martin, M.B. Kovac, S. Humphray, A. Lucassen, C.C. Holmes, D. Bentley, P. Donnelly, J. Taylor, C. Petridis, R. Roylance, E.J. Sawyer, D.J. Kerr, S. Clark, J. Grimes, S.E. Kearsey, H.J.W. Thomas, G. McVean, R.S. Houlston, I. Tomlinson, Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 45, 136–144 (2013)

    Article  PubMed  CAS  Google Scholar 

  21. M.M. Hahn, R.M. de Voer, N. Hoogerbrugge, M.J.L. Ligtenberg, R.P. Kuiper, A. Geurts van Kessel, The genetic heterogeneity of colorectal cancer predisposition - guidelines for gene discovery. Cell. Oncol. 39, 491–510 (2016)

    Article  CAS  Google Scholar 

  22. D. Chubb, P. Broderick, S.E. Dobbins, M. Frampton, B. Kinnersley, S. Penegar, A. Price, Y.P. Ma, A.L. Sherborne, C. Palles, M.N. Timofeeva, D.T. Bishop, M.G. Dunlop, I. Tomlinson, R.S. Houlston, Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. Nat. Commun. 7, 11883 (2016)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. K. El Bairi, A.H. Kandhro, A. Gouri, W. Mahfoud, N. Louanjli, B. Saadani, S. Afqir, M. Amrani, Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer. Cell. Oncol. 40, 105–118 (2017)

    Article  CAS  Google Scholar 

  24. A. Chavez-Gonzalez, B. Bakhshinejad, K. Pakravan, M.L. Guzman, S. Babashah, Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer. Cell. Oncol. 40, 1–20 (2017)

    Article  CAS  Google Scholar 

  25. M. Yousefi, T. Bahrami, A. Salmaninejad, R. Nosrati, P. Ghaffari, S.H. Ghaffari, Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options. Cell. Oncol. 40, 419–441 (2017)

    Article  CAS  Google Scholar 

  26. P.O. Pietarinen, C.A. Eide, P. Ayuda-Durán, S. Potdar, H. Kuusanmäki, E.I. Andersson, J.P. Mpindi, T. Pemovska, M. Kontro, C.A. Heckman, O. Kallioniemi, K. Wennerberg, H. Hjorth-Hansen, B.J. Druker, J.M. Enserink, J.W. Tyner, S. Mustjoki, K. Porkka, Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors. Oncotarget 8, 22606–22615 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  27. J. Tang, L. Karhinen, T. Xu, A. Szwajda, B. Yadav, K. Wennerberg, T. Aittokallio, Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways. PLoS Comput. Biol. 9, e1003226 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. B. Yadav, T. Pemovska, A. Szwajda, E. Kulesskiy, M. Kontro, R. Karjalainen, M.M. Majumder, D. Malani, A. Murumägi, J. Knowles, K. Porkka, C. Heckman, O. Kallioniemi, K. Wennerberg, T. Aittokallio, Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Sci. Rep. 4, 5193 (2015)

    Article  CAS  Google Scholar 

  29. H. Kuusanmäki, O. Dufva, E. Parri, A.J. van Adrichem, H. Rajala, M.M. Majumder, B. Yadav, A. Parsons, W.C. Chan, K. Wennerberg, S. Mustjoki, C.A. Heckman, Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling. Oncotarget 8, 97516–97527 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  30. R. Demsky, J. McCuaig, M. Maganti, K.J. Murphy, B. Rosen, S.R. Armel, Keeping it simple: Genetics referrals for all invasive serous ovarian cancers. Gynecol. Oncol. 130, 329–333 (2013)

    Article  PubMed  CAS  Google Scholar 

  31. A. Lanceley, Z. Eagle, G. Ogden, S. Gessler, K. Razvi, J.A. Ledermann, L. Side, Family history and women with ovarian cancer. Int. J. Gynecol. Cancer 22, 254–259 (2012)

    Article  PubMed  Google Scholar 

  32. A. George, D. Riddell, S. Seal, S. Talukdar, S. Mahamdallie, E. Ruark, V. Cloke, I. Slade, Z. Kemp, M. Gore, A. Strydom, S. Banerjee, H. Hanson, N. Rahman, Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Sci. Rep. 6, 29506 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  33. Guidance and guidelines, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. NICE [Internet]. United Kingdom, National Institute for Health and Clinical Excellence. https://www.nice.org.uk/guidance/cg164/chapter/Recommendations Accessed 11 December 2017

  34. I. Slade, H. Hanson, A. George, K. Kohut, A. Strydom, S. Wordsworth, N. Rahman, A cost analysis of a cancer genetic service model in the UK. J. Community Genet. 7, 185–194 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  35. Assembly of the Republic, in Diário da República Eletrónico, Legislação, Lei n.o 12/2005- Diário da República n.o 18/2005, Série I-A de 2005–01-26- DRE. 606–611 [Internet]. Portugal, Diário da República Eletrónico. https://dre.pt/web/guest/pesquisa/-/search/624463/details/normal?_search_WAR_drefrontofficeportlet_print_preview=print-preview Accessed 11 December 2017

  36. Assembly of the Republic, in Diário da República Eletrónico, Legislação, Decreto-Lei n.o 131/2014 – Ministério da Saúde–Regulamenta a Lei n.o 12/2005, de 26 de janeiro [Internet]. Portugal, Diário da República Eletrónico. http://direitodamedicina.sanchoeassociados.com/arquivo/decreto-lei-n-o-1312014-ministerio-da-saude-regulamenta-a-lei-n-o-122005-de-26-de-janeiro-no-que-se-refere-a-protecao-e-confidencialidade-da-informacao-genetica-as-bases-de-da/ Accessed 11 December 2017

  37. Commissioner of the Press Announcements in FDA, U.S. Food and Drug, Press Announcements. FDA approves first cancer treatment for any solid tumor with a specific genetic feature [Internet]. USA, FDA. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm Accessed 11 December 2017

  38. D.T. Le, J.N. Uram, H. Wang, B.R. Bartlett, H. Kemberling, A.D. Eyring, A.D. Skora, B.S. Luber, N.S. Azad, D. Laheru, B. Biedrzycki, R.C. Donehower, A. Zaheer, G.A. Fisher, T.S. Crocenzi, J.J. Lee, S.M. Duffy, R.M. Goldberg, A. de la Chapelle, M. Koshiji, F. Bhaijee, T. Huebner, R.H. Hruban, L.D. Wood, N. Cuka, D.M. Pardoll, N. Papadopoulos, K.W. Kinzler, S. Zhou, T.C. Cornish, J.M. Taube, R.A. Anders, J.R. Eshleman, B. Vogelstein, L.A. Diaz, PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372, 2509–2520 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. D.T. Le, J.N. Durham, K.N. Smith, H. Wang, B.R. Bartlett, L.K. Aulakh, S. Lu, H. Kemberling, C. Wilt, B.S. Luber, F. Wong, N.S. Azad, A.A. Rucki, D. Laheru, R. Donehower, A. Zaheer, G.A. Fisher, T.S. Crocenzi, J.J. Lee, T.F. Greten, A.G. Duffy, K.K. Ciombor, A.D. Eyring, B.H. Lam, A. Joe, S.P. Kang, M. Holdhoff, L. Danilova, L. Cope, C. Meyer, S. Zhou, R.M. Goldberg, D.K. Armstrong, K.M. Bever, A.N. Fader, J. Taube, F. Housseau, D. Spetzler, N. Xiao, D.M. Pardoll, N. Papadopoulos, K.W. Kinzler, J.R. Eshleman, B. Vogelstein, R.A. Anders, L.A. Diaz, Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357, 409–413 (2017)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. M. Robson, S.A. Im, E. Senkus, B. Xu, S.M. Domchek, N. Masuda, S. Delaloge, W. Li, N. Tung, A. Armstrong, W. Wu, C. Goessl, S. Runswick, P. Conte, Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017)

    Article  PubMed  CAS  Google Scholar 

  41. European public assessment report (EPAR) in European Medicines Agency (EMA), Science Medicines Health, Human Medicine. Lynparza [Internet]. United Kingdom, EMA. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003726/human_med_001831.jsp&mid=WC0b01ac058001d124 Accessed 15 December 2017

  42. F.R. Vogenberg, C. Isaacson Barash, M. Pursel, Personalized medicine: part 1: evolution and development into theranostics. P & T 35, 560–576 (2010)

  43. Serviço Nacional de Saúde (SNS), Medicina personalizada na Europa [Internet]. Portugal, SNS. https://www.sns.gov.pt/noticias/2017/10/20/medicina-personalizada-na-europa/ Accessed 18 December 2017

  44. N.L. Bragazzi, From P0 to P6 medicine, a model of highly participatory, narrative, interactive, and "augmented" medicine: some considerations on Salvatore Iaconesi’s clinical story. Patient Prefer Adherence 7, 353–359 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  45. E.P. Bottinger, Foundations, promises and uncertainties of personalized medicine. Mt Sinai J. Med. 74, 15–21 (2007)

    Article  PubMed  Google Scholar 

  46. M.A. Hamburg, F.S. Collins, The path to personalized medicine. N. Engl. J. Med. 363, 301–304 (2010)

    Article  PubMed  CAS  Google Scholar 

  47. M.F. Haward, J.M. Lorenz, Communicating risk under conditions of uncertainty: not as simple as it may seem. Acta Paediatr. 100, 651–652 (2011)

    Article  PubMed  Google Scholar 

  48. N.J. Schork, Personalized medicine: time for one-person trials. Nature 520, 609–611 (2015)

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology and Biochemistry, Springer Science + Business Media B.V, Van Godewijckstraat 30, 3311, GX, Dordrecht, The Netherlands

    Inês Teles Siefers Alves

  2. Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal

    Manuel Condinho, Bruna F. Pereira, Rafael Fernandes, Vânia Gonçalves, Paulo J. da Costa, Rafaela Lacerda, Ana Rita Marques, Patrícia Martins-Dias, Gonçalo R. Nogueira, Ana Rita Neves, Joana Silva & Luísa Romão

  3. Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisbon, Lisbon, Portugal

    Manuel Condinho, Bruna F. Pereira, Rafael Fernandes, Vânia Gonçalves, Paulo J. da Costa, Rafaela Lacerda, Ana Rita Marques, Patrícia Martins-Dias, Gonçalo R. Nogueira, Ana Rita Neves, Joana Silva & Luísa Romão

  4. Medical Genetics Service, Pediatric Department, Hospital Santa Maria, Lisbon, Portugal

    Sónia Custódio, Raquel Rodrigues, Eva Rolo, André Travessa & Ana Sousa

  5. Genetics Laboratory, Hospital Center of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Patrícia Pinho & Rosário Pinto Leite

Authors
  1. Inês Teles Siefers Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel Condinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sónia Custódio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruna F. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rafael Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vânia Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paulo J. da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rafaela Lacerda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ana Rita Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Patrícia Martins-Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gonçalo R. Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ana Rita Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Patrícia Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Raquel Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Eva Rolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Joana Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. André Travessa
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Rosário Pinto Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ana Sousa
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Luísa Romão
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Inês Teles Siefers Alves.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alves, I.T.S., Condinho, M., Custódio, S. et al. Genetics of personalized medicine: cancer and rare diseases. Cell Oncol. 41, 335–341 (2018). https://doi.org/10.1007/s13402-018-0379-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-018-0379-3

Keywords

Search

Navigation