Advertisement

Molecular biology as a tool for the treatment of cancer

  • Carla de Castro Sant’ Anna
  • Alberto Gomes Ferreira Junior
  • Paulo Soares
  • Fabricio Tuji
  • Eric Paschoal
  • Luiz Cláudio Chaves
  • Rommel Rodriguez Burbano
Review Article

Abstract

Cancer is a genetic disease characterized by uncontrolled cell growth and metastasis. Cancer can have a number of causes, such the activation of oncogenes, the inactivation of tumor-suppressing genes, mutagenesis provoked by external factors, and epigenetic modifications. The development of diagnostic tools and treatments using a molecular biological approach permits the use of sensitive, low-cost, noninvasive tests for cancer patients. Biomarkers can be used to provide rapid, personalized oncology, in particular the molecular diagnosis of chronic myeloid leukemia, and gastric, colon, and breast cancers. Molecular tests based on DNA methylation can also be used to direct treatments or evaluate the toxic effects of chemotherapy. The adequate diagnosis, prognosis, and prediction of the response of cancer patients to treatment are essential to ensure the most effective therapy, reduce the damaging effects of treatment, and direct the therapy to specific targets, and in this context, molecular biology has become increasingly important in oncology. In this brief review, we will demonstrate the fundamental importance of molecular biology for the treatment of three types of cancer—chronic myeloid leukemia, hereditary diffuse gastric cancer, and astrocytomas (sporadic tumors of the central nervous system). In each of these three models, distinct biological mechanisms are involved in the transformation of the cells, but in all cases, molecular biology is fundamental to the development of personalized analyses for each patient and each type of neoplasia, and to guarantee the success of the treatment.

Keywords

Biomarkers Epigenetics Molecular biology Cancer 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

As the review study did not include any personal data, the Ophir Loyola Hospital does not require submission to the ethics in research committee or any other form of institutional review.

Informed consent

As this manuscript is a literature review, informed consent is not applicable.

References

  1. 1.
    Knudson AG. Overview. Genes that predispose to cancer. Mutat Res. 1991;247:185–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Martincorena I, Campbell PJ. Somatic mutation in cancer and normal cells. Science. 2016;351(6277):1483–8.Google Scholar
  3. 3.
    Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet. 1993;9:138–41.PubMedCrossRefGoogle Scholar
  4. 4.
    Von Hansemann D. Ueber asymmetrische Zelltheilung in Epithelhresbsen und deren biologische bedeutung. Virchows Arch A Pathol Anat. 1890;119:299–326.CrossRefGoogle Scholar
  5. 5.
    Boveri T. Zur Frage der Entstehung maligner Tumoren. Jena: Publisher G Fischer; 1914. p. 64.Google Scholar
  6. 6.
    Manchester KL. Theodor Boveri and the origin of malignant tumours. Trends Cell Biol. 1995;5(10):384–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science. 1960;132:1497.Google Scholar
  8. 8.
    Baltzer F. Theodor Boveri. Science. 1964;144:809–15.PubMedCrossRefGoogle Scholar
  9. 9.
    Lander ES, International Human Genome Sequencing Consortium, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.PubMedCrossRefGoogle Scholar
  10. 10.
    Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291:1304–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Loeb KR, Loeb LA. Significance of multiple mutations in cancer. Carcinogenesis. 2000;21(3):379–85.PubMedCrossRefGoogle Scholar
  13. 13.
    Barak V, Meirovitz A, Leibovici V, et al. The diagnostic and prognostic value of tumor markers (CEA, SCC, CYFRA 21-1, TPS) in head and neck cancer patients. Anticancer Res. 2015;35(10):5519–24.PubMedGoogle Scholar
  14. 14.
    Kazarian A, Blyuss O, Metodieva G, et al. Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples. Br J Cancer. 2017;116(4):501–8.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Chistiakov DA, Myasoedova VA, Grechko AV, Melnichenko AA, Orekhov AN. New biomarkers for diagnosis and prognosis of localized prostate cancer. Semin Cancer Biol. 2018;17:30288-2.Google Scholar
  16. 16.
    Witte ON. Role of the BCR-ABL oncogene in human leukemia: fifteenth Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1993;53:485–9.PubMedGoogle Scholar
  17. 17.
    Grossmann V, Kohlmann A, Zenger M, et al. A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia. 2011;25:557–61.PubMedCrossRefGoogle Scholar
  18. 18.
    Branford S. Monitoring after successful therapy for chronic myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2012;2012:105–10.PubMedGoogle Scholar
  19. 19.
    Hantschel O, Grebien F, Superti-Furga G. The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL. Cancer Res. 2012;72:4890–5.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Holyoake TL, Vetrie D. The chronic myeloid leukemia stem cell: stemming the tide of persistence. Blood. 2017;129:1595–606.PubMedCrossRefGoogle Scholar
  21. 21.
    Kujak C, Kolesar JM. Treatment of chronic myelogenous leukemia. Am J Health Syst Pharm. 2016;73:113–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Baccarani M, Deininger M, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood. 2013;122:872–84.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Morotti A, Fava C, Saglio G. Milestones and Monitoring. Curr Hematol Malig Rep. 2015;10:167–72.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    NCCN. Clinical practice guidelines in oncology: chronic myelogenous leukemia. Version 1. 2016. http://www.nccn.org. Accessed 19 June 2018.
  25. 25.
    Goldman JM. Chronic myeloid leukemia: a historical perspective. Semin Hematol. 2010;47:302–11.PubMedCrossRefGoogle Scholar
  26. 26.
    Goldman JM, Melo JV. Chronic myeloid leukemia—advances in biology and new approaches to treatment. New Engl J Med. 2003;349:1451–64.PubMedCrossRefGoogle Scholar
  27. 27.
    Marum JE, Branford S. Current developments in molecular monitoring in chronic myeloid leukemia. Ther Adv Hematol. 2016;7:237–51.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Deininger MW. Molecular monitoring in CML and the prospects for treatment-free remissions. Hematol Am Soc Hematol Educ Progr. 2015;2015:257–63.Google Scholar
  29. 29.
    Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096–102.PubMedCrossRefGoogle Scholar
  31. 31.
    Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Muller MC, Saglio G, Lin F, et al. An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007;92:970–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Cross NC, White HE, Muller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012;26:2172–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029–35.PubMedCrossRefGoogle Scholar
  35. 35.
    Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122:515–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:424–30.CrossRefGoogle Scholar
  37. 37.
    Sweet K, Zhang L, Pinilla-Ibarz J. Biomarkers for determining the prognosis in chronic myelogenous leukemia. J Hematol Oncol. 2013;6(54):1–9.Google Scholar
  38. 38.
    Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–41.PubMedCrossRefGoogle Scholar
  39. 39.
    Lopes NR, Abreu MTCL. Inibidores de tirosino quinase na leucemia mieloide crônica. Rev Bras Hematol Hemoter. 2009;31:449–53.CrossRefGoogle Scholar
  40. 40.
    Gruber FX, Ernst T, Porkka K, et al. Dynamics of the emergence of dasatinib and nilotinib resistance in imatinib-resistante CML patients. Leukemia. 2012;26(1):172–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Saglio G, Fava C. BCR-ABL1 mutation not equal ponatinib resistance. Blood. 2016;127(6):666–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Lei H, Jin J, Liu M, et al. Chk1 inhibitors overcome imatinib resistance in chronic myeloid leukemia cells. Leuk Res. 2018;64:17–23.PubMedCrossRefGoogle Scholar
  43. 43.
    Golas JM, Arndt K, Etienne C, et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 2003;63:375–81.PubMedGoogle Scholar
  44. 44.
    Remsing Rix LL, Rix U, Colinge J, et al. Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009;23:477–85.PubMedCrossRefGoogle Scholar
  45. 45.
    Gambacorti-Passerini C, Brummendorf TH, Kim DW, et al. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: minimum 24-month follow-up. Am J Hematol. 2014;89:732–42.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Isfort S, Brümmendorf TH. Bosutinib in chronic myeloid leukemia: patient selection and perspectives. J Blood Med. 2018;9:43–50.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Müller MC, Cervantes F, Hjorth-Hansen H, Janssen JJWM, Milojkovic D, Rea D, Rosti G. Ponatinib in chronic myeloid leukemia (CML): consensus on patient treatment and management from a European expert panel. Crit Rev Oncol Hematol. 2017;120:52–9.PubMedCrossRefGoogle Scholar
  48. 48.
    O’Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009;16:401–12.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Cortes JE, Kim DW, Pinilla-Ibarz J. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. New Engl J Med. 2013;369:1783–96.PubMedCrossRefGoogle Scholar
  50. 50.
    Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Investig. 2011;121(1):396–409.PubMedCrossRefGoogle Scholar
  51. 51.
    Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007;109(1):58–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Shah NP, Kantarjian HM, Kim DW, Réa D, DorlhiacLlacer PE, Milone JH, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008;26(19):3204–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129:846–54.PubMedCrossRefGoogle Scholar
  54. 54.
    Legros L, Nicolini FE, Etienne G, et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer. 2017;123:4403–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Rea D, Cavuela JM. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol 2017.  https://doi.org/10.1007/s12185-017-2295-0 PubMedCrossRefGoogle Scholar
  56. 56.
    Laneuville P. Stopping second-generation TKIs in CML. Blood. 2017;129(7):805–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after 3 treatment discontinuation: the KID study. Haematologica. 2016;101(6):717–23.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Soverini S, Hochhaus A, Nicolini FE, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011;118(5):1208–15.PubMedCrossRefGoogle Scholar
  59. 59.
    Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8:1018–29.PubMedCrossRefGoogle Scholar
  60. 60.
    Liu X, Kung A, Malinoski B, Prakash GK, Zhang C. Development of alkyne-containing pyrazolopyrimidines to overcome drug resistance of Bcr-Abl kinase. J Med Chem. 2015;58(23):9228–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. Am J Hematol. 2016;91(2):252–65.PubMedCrossRefGoogle Scholar
  62. 62.
    Cheetham GM, Charlton PA, Golec JM, Pollard JR. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett. 2007;251:323–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Pollard JR, Mortimore M. Discovery and development of aurora kinase inhibitors as anticancer agents. J Med Chem. 2009;52:2629–51.PubMedCrossRefGoogle Scholar
  64. 64.
    Seymour JF, Kim DW, Rubin E, et al. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Cancer J. 2014;4(e238):1–6.Google Scholar
  65. 65.
    Yan M, Wang C, He B, et al. Aurora-A kinase: a potent oncogene and target for cancer therapy. Med Res Rev. 2016;36:1036–79.PubMedCrossRefGoogle Scholar
  66. 66.
    Afonso O, Figueiredo AC, Maiato H. Late mitotic functions of Aurora kinases. Chromosoma. 2017;126:93–103.PubMedCrossRefGoogle Scholar
  67. 67.
    Carter TA, Wodicka LM, Shah NP, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA. 2005;102(31):11011–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood. 2007;109(2):500–2.PubMedCrossRefGoogle Scholar
  69. 69.
    Akahane D, Tauchi T, Okabe S, Nunoda K, Ohyashiki K. Activity of a novel Aurora kinase inhibitor against the T315I mutant form of BCR-ABL: in vitro and in vivo studies. Cancer Sci. 2008;99:1251–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Yaghoobi M, Rakhshani N, Sadr F, et al. Hereditary risk factors for the development of gastric cancer in younger patients. BMC Gastroenterol. 2004;4(28):1–7.Google Scholar
  71. 71.
    Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. New Engl J Med. 2014;371:497–506.PubMedCrossRefGoogle Scholar
  72. 72.
    Imyanitov EN, Moiseyenko VM. Drug therapy for hereditary cancers. Hered Cancer Clin Pract. 2011;9:1–16.CrossRefGoogle Scholar
  73. 73.
    Dantas ELR, Sá FHL, Carvalho SMF, Arruda AP, Ribeiro EM, Ribeiro EM. Genética do Câncer Hereditário. Rev Bras de Cancerol. 2009;55:263–9.Google Scholar
  74. 74.
    Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER cancer statistics review, 1975–2013. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016. Accessed 10 Mar 2018.
  75. 75.
    Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392:402–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Dunbier A, Guilford P. Hereditary diffuse gastric cancer. Adv Cancer Res. 2001;83:55–65.PubMedCrossRefGoogle Scholar
  77. 77.
    Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: a report of a family and review of the literature. EJSO. 2005;31:259–64.PubMedCrossRefGoogle Scholar
  78. 78.
    Hansford S, Kaurah P, Li-Chang H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 2015;1(1):23–32.PubMedCrossRefGoogle Scholar
  79. 79.
    Feroce I, Serrano D, Biffi R, et al. Hereditary diffuse gastric cancer in two families: a case report. Oncol Lett. 2017;14:1671–4.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Oliveira C, Suriano G, Ferreira P, et al. Genetic screening for familial gastric cancer. Hered Cancer Clin Pract. 2004;2:51–64.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Assumpção PP, Burbano, RR Genética Do Câncer Gástrico In: Linhares E, Lourenço, Sano T (eds) Atualização em Câncer Gástrico. Tecmedd: Ribeirão Preto; 2005. pp. 95-108Google Scholar
  82. 82.
    Caldas C, Carneiro F, Lynch HT, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36:873–80.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Fitzgerald RC, Hardwick R, Huntsman D, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47:436–44.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Gumbiner B, Stevenson B, Grimaldi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol. 1988;107:1575–87.PubMedCrossRefGoogle Scholar
  85. 85.
    Green KJ, Getsios S, Troyanovsky S, Godsel LM. Intercellular junction assembly, dynamics, and homeostasis. Cold Spring Harb Perspect Biol. 2010;2(2):1–22.CrossRefGoogle Scholar
  86. 86.
    Mateus AR, Simões-Correia J, Figueiredo J, et al. E-cadherin mutations and cell motility: a genotype–phenotype correlation. Exp Cell Res. 2009;315:1393–402.PubMedCrossRefGoogle Scholar
  87. 87.
    Ghaffari SR, Rafati M, Sabokbar T, Dastan J. A novel truncating mutation in the E-cadherin gene in the first Iranian family with hereditary diffuse gastric cancer. EJSO. 2010;36:559–62.PubMedCrossRefGoogle Scholar
  88. 88.
    Mayrbaeurla B, Kellerf G, Schauerb W, et al. Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members. Eur J Gastroenterol Hepatol. 2010;22:306–10.CrossRefGoogle Scholar
  89. 89.
    Van der Post RS, Vogelaar IP, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;52(6):361–74.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Zylberberg HM, Sultan K, Rubin S. Hereditary diffuse gastric cancer: one family’s story. World J Clin Cases. 2018;6(1):1–5.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Knudson AG Jr. Prince Takamatsu memorial lecture. Rare cancers: clues to genetic mechanisms. Princess Takamatsu Symp. 1987;18:221–31.PubMedGoogle Scholar
  92. 92.
    Chen LC, Kurisu W, Ljung BM, Goldman ES, Moore D 2nd, Smith HS. Heterogeneity for allelic loss in human breast cancer. J Natl Cancer Inst. 1992;84:506–10.PubMedCrossRefGoogle Scholar
  93. 93.
    Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16:e60–70.PubMedCrossRefGoogle Scholar
  94. 94.
    Corso G, Marrelli D, Pascale V, Vindigni C, Roviello F. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer. 2012;12(8):1–10.Google Scholar
  95. 95.
    Fitzgerald RC, Caldas C. E-cadherin mutations and hereditary gastric cancer: prevention by resection? Dig Dis. 2002;20:23–31.PubMedCrossRefGoogle Scholar
  96. 96.
    Guilford P, Humar B, Blair V. Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice. Gastric Cancer. 2010;13:1–10.PubMedCrossRefGoogle Scholar
  97. 97.
    Corso G, Roviello F, Paredes J, et al. Characterization of the P373L E-cadherin germline missense mutation and implication for clinical management. EJSO. 2007;33:1061–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Shinmura K, Kohno T, Takahashi M, et al. Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations. Carcinogenesis. 1999;20:1127–31.PubMedCrossRefGoogle Scholar
  99. 99.
    Oliveira C, Bordin MC, Grehan N, et al. Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum Mutat. 2002;19:510–7.PubMedCrossRefGoogle Scholar
  100. 100.
    Moreira-Nunes CA, Barros MB, do Nascimento Borges B, et al. Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil. Hered Cancer Clin Pract. 2014;12(1):1–8.CrossRefGoogle Scholar
  101. 101.
    Figueiredo C, Machado JC, Pharoah P, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst. 2002;94:1680–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Machado JC, Figueiredo C, Canedo P, et al. A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology. 2003;125:364–71.PubMedCrossRefGoogle Scholar
  103. 103.
    Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet. 2000;26:16–7.PubMedCrossRefGoogle Scholar
  104. 104.
    Van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65:3756–88.PubMedCrossRefGoogle Scholar
  105. 105.
    Carvalho S, Catarino TA, Dias AM, et al. Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer. Oncogene. 2016;35(13):1619–31.PubMedCrossRefGoogle Scholar
  106. 106.
    Hannon GJ, Rivas FV, Murchison EP, Steitz JA. The expanding universe of noncoding RNAs. Cold Spring Harb Symp Quant Biol. 2006;71:551–64.PubMedCrossRefGoogle Scholar
  107. 107.
    Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41:10–3.PubMedCrossRefGoogle Scholar
  109. 109.
    Laird PW. Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet. 2010;11(3):191–203.PubMedCrossRefGoogle Scholar
  110. 110.
    Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68.PubMedCrossRefGoogle Scholar
  111. 111.
    Virani S, Colacino JA, Kim JH, Rozek LS. Cancer epigenetics: a brief review. ILAR J. 2012;53:359–69.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Santos JC, Ribeiro ML. Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis. World J Gastroenterol. 2015;21:9021–37.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Villano JL, Seery TE, Bressler LR. Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 2009;64:647–55.PubMedCrossRefGoogle Scholar
  114. 114.
    Roy S, Lahiri D, Maji T, Biswas J. Recurrent Glioblastoma: where we stand. South Asian J Cancer. 2015;4:163–73.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Riemenschneider MJ, Hegi ME, Reifenberger G. MGMT promoter methylation in malignant gliomas. Target Oncol. 2010;5(3):161–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Jordan JT, Gerstner ER, Batchelor TT, Cahill DP, Plotkin SR. Glioblastoma care in the elderly. Cancer. 2016;122:189–97.PubMedCrossRefGoogle Scholar
  117. 117.
    Weller M, Stupp R, Reifenberger G, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6(1):39–51.PubMedCrossRefGoogle Scholar
  118. 118.
    Trindade V, Picarelli H, Figueiredo EG, Teixeira MJ. Gliomas: marcadores tumorais e prognóstico. Arq Bras Neurocir. 2012;31:91–4.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Carla de Castro Sant’ Anna
    • 1
    • 2
  • Alberto Gomes Ferreira Junior
    • 1
  • Paulo Soares
    • 1
  • Fabricio Tuji
    • 1
  • Eric Paschoal
    • 1
  • Luiz Cláudio Chaves
    • 1
  • Rommel Rodriguez Burbano
    • 1
  1. 1.Laboratory of Molecular BiologyOphir Loyola HospitalBelémBrazil
  2. 2.João de Barros Barreto University HospitalBelémBrazil

Personalised recommendations