Evolución de la genómica tumoral
DOI:
https://doi.org/10.56050/01205498.1566Palabras clave:
Cáncer, genómica, medicina de precisión, biomarcador, ADN, mutaciónResumen
La comprensión de que la progresión del cáncer requería la interacción de múltiples genes proporcionó una de las razones fundamentales, para embarcarse en 1986, en el proyecto genoma humano. Solo con una secuencia del genoma de referencia podría entenderse el espectro completo de cambios somáticos que conducen al cáncer. Desde su finalización en 2003, la secuencia del genoma humano de referencia ha cumplido su promesa como herramienta fundamental para esclarecer la patogénesis de diversas neoplasias. Los recientes avances biotecnológicos han llevado a la identificación de características biológicas complejas y únicas asociadas con la carcinogénesis. La perfilación del ADN tumoral libre circulante y de las células neoplásicas, así como de factores relacionados con inmunidad, análisis de proteinas y del ARN, permiten optimizar el diagnóstico y tratamiento del cáncer. En consecuencia, la búsqueda de respuestas con base en experimentos clínicos ha evolucionado, pasando de los estudios centrados en un tipo específico de tumor a una o muchas características genómicas, independientes de la histología, y con base en diseños innovadores y adaptativos. A continuación, revisamos los hitos y conceptos históricos clave en la genómica del cáncer y algunos de los descubrimientos novedosos en esta área.
Biografía del autor/a
Andrés F. Cardona
MD MSc PhD. Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer – FICMAC, Bogotá, Colombia.
Grupo de Investigación en Oncología Molecular y Sistemas Biológicos (FoxG), Universidad El Bosque, Bogotá, Colombia.
Oscar Arrieta, Instituto Nacional de Cancerología – INCaN, Ciudad de México
Sección Oncología Torácica y Laboratorio de Medicina Personalizada del Cáncer, Instituto Nacional de Cancerología – INCaN, Ciudad de México, México.
Zyania Lucía Zatarain-Barron, Instituto Nacional de Cancerología – INCaN, Ciudad de México
Sección Oncología Torácica y Laboratorio de Medicina Personalizada del Cáncer, Instituto Nacional de Cancerología – INCaN, Ciudad de México, México.
Christian Rolfo, Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer
MD MSc PhD. Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer – FICMAC, Bogotá, Colombia.
Departamento Oncología Clínica, Marlene and Stewart Greenebaum Comprehensive Cancer Center, Facultad de Medicina Universidad de Maryland, Baltimore, Maryland, Estados Unidos.
Camila Ordoñez, Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer
MD. Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer – FICMAC, Bogotá, Colombia.
Alejandro Ruíz Patiño, Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer
MD MSc PhD. Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer – FICMAC, Bogotá, Colombia.
Grupo de Investigación en Oncología Molecular y Sistemas Biológicos (FoxG), Universidad El Bosque, Bogotá, Colombia.
Grupo de Investigación en Oncología Molecular y Sistemas Biológicos (FoxG), Universidad El Bosque, Bogotá, Colombia.
Referencias bibliográficas
1. Dulbecco R. A turning point in cancer research: sequencing the human genome. Science. 1986; 231(4742): 1055-6.
2. Robertson M. The proper study of mankind. Nature. 1986; 322(6074):11.
3. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev Cancer. 2004; 4(3):177-83.
4. Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013; 339(6127): 1546–1558.
5. Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol. 2007;1(1):26–41.
6. Sadikovic B, Al-Romaih K, Squire JA, Zielenska M. Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics.2008;9(6):394–408.
7. Stankiewicz P, Lupski JR. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61:437–455.
8. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini G, Guilhot BJ et al. Imatinib induces durable hemato-logic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928–1937.
9. Eckschlager T, Pilat D, Kodet R, et al. DNA ploidy in neuroblastoma. Neo-plasma. 1996;43(1):23–26.
10. Mandahl N, Gustafson P, Mertens F, et al. Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer. 2002;33(2):188–200.
11. Orr LC, Fleitz J, McGavran L, et al. Cytogenetics in pediatric low-grade astrocytomas. Med Pediatr Oncol. 2002;38(3):173–177.
12. Biswas S, Rao CM. Epigenetics in cancer: fundamentals and beyond. Pharmacol Ther. 2017;173:118–134.
13. Chen ZX, Riggs AD. DNA methylation and demethylation in mammals. J Biol Chem. 2011;286(21):18347–18353.
14. Chakravarthi BV, Nepal S, Varambally S. Genomic and epigenomic alterations in cancer. Am J Pathol. 2016;186(7):1724–1735.
15. Weisenberger DJ. Characterizing DNA methylation alterations from The Cancer Genome Atlas. J Clin Invest. 2014;124(1):17–23.
16. Zhao R, Choi BY, Lee MH, et al. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EBioMedicine. 2016;8:30–39.
17. Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15:38.
18. Chakraborty C, Sharma AR, Sharma G, et al. The novel strategies for next-generation cancer treatment: miRNA combined with chemotherapeutic agents for the treatment of cancer. Oncotarget. 2018;9(11):10164– 10174.
19. Dizdaroglu M. Oxidatively induced DNA damage and its repair in cancer. Mutat Res Rev Mutat Res. 2015;763:212–245.
20. Feinberg AP, Koldobskiy MA, Gondor A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet. 2016;17(5):284–299.
21. Wallace SS, Murphy DL, Sweasy JB. Base excision repair and cancer. Cancer Lett. 2012;327(1–2):73–89.
22. Kim YJ, Wilson DM, 3rd. Overview of base excision repair biochemistry. Curr Mol Pharmacol. 2012;5(1):3–13.
23. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–413.
24. Li SKH, Martin A. Mismatch repair and colon cancer: mechanisms and therapies explored. Trends Mol Med. 2016;22(4):274–289.
25. Helleday T, Eshtad S, Nik-Zainal S. Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet. 2014;15(9):585–598.
26. Aparicio T, Baer R, Gautier J. DNA double-strand break repair pathway choice and cancer. DNA Repair (Amst). 2014;19:169–175.
27. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Nonhomologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol. 2017;18(8):495–506.
28. Katsanis SH, Katsanis N. Molecular genetic testing and the future of clinical genomics. Nat Rev Genet. 2013;14(6):415–426.
29. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev Cancer. 2004 ; 4(3):177-83.
30. Tokheim CJ, Papadopoulos N, Kinzler KW, et al. Evaluating the evaluation of cancer driver genes. Proc Natl Acad Sci U S A. 2016;113(50):14330-14335..
31. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008; 321(5897):1807-12.
32. Hou AH, Tien HF. Genomic landscape in acute myeloid leukemia and its implications in risk classification and targeted therapies. J Biomed Sci. 202021;27(1):81.
33. Chen G, Cai Z, Dong X, et al. Genomic and Transcriptomic Landscape of Tumor Clonal Evolution in Cholangiocarcinoma. Front Genet. 2020;11:195.
34. Yang H, Ye D, Guan KL, et al. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res. 2012;18(20):5562-71.
35. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424-33.
36. Varela I, Tarpey P, Raine K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011;469(7331):539-42.
37. Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS One. 2013; 8(1):e55119.
38. Kobrinski DA, Yang H, Kittaneh M. BAP1: role in carcinogenesis and clinical implications. Transl Lung Cancer Res. 2020;9(Suppl 1):S60-S66.
39. Li Y, Shi J, Yang J, et al. Uveal melanoma: progress in molecular biology and therapeutics. Ther Adv Med Oncol. 2020 Oct 22;12:1758835920965852.
40. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64-9.
41. Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81-94.
42. Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013;501(7467):338-45.
43. Turner NC, Reis-Filho JS. Genetic heterogeneity and cancer drug resistance. Lancet Oncol. 2012 ;13(4):e178- 85. Mar 30.
44. Venkatesan S, Swanton C, Taylor BS, Costello JF. Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution. Cold Spring Harb Perspect Med. 2017;7(8):a026617.
45. Zhang Y, Ma Y, Li Y, et al. Comparative analysis of cooccurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations. J Cancer Res Clin Oncol. 2019;145(3):747- 757.
46. Ljungman M, Lane DP. Transcription - guarding the genome by sensing DNA damage. Nat Rev Cancer. 2004;4(9):727-37.
47. Perrimon N, Pitsouli C, Shilo BZ. Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb Perspect Biol. 2012;4(8):a005975.
48. Baish JW, Stylianopoulos T, Lanning RM, Kamoun WS, Fukumura D, Munn L et al. Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A. 2011; 108(5):1799-803.
49. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010; 10(2):116-29.
50. Yun J, Rago C, Cheong I, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009; 325(5947):1555-9.
51. Medema RH, Macůrek L. Checkpoint control and cancer. Oncogene. 2012; 31(21):2601-13.
52. Bertier G, Carrot-Zhang J, Ragoussis V, Joly Y. Integrating precision cancer medicine into healthcare—policy, practice, and research challenges. Genome Med. 2016; 8(1):108.
53. Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12(1): 8.
54. McLeod HL. Cancer pharmacogenomics: early promise, but concerted effort needed. Science. 2013; 339(6127):1563-6.
2. Robertson M. The proper study of mankind. Nature. 1986; 322(6074):11.
3. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev Cancer. 2004; 4(3):177-83.
4. Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013; 339(6127): 1546–1558.
5. Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol. 2007;1(1):26–41.
6. Sadikovic B, Al-Romaih K, Squire JA, Zielenska M. Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics.2008;9(6):394–408.
7. Stankiewicz P, Lupski JR. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61:437–455.
8. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini G, Guilhot BJ et al. Imatinib induces durable hemato-logic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928–1937.
9. Eckschlager T, Pilat D, Kodet R, et al. DNA ploidy in neuroblastoma. Neo-plasma. 1996;43(1):23–26.
10. Mandahl N, Gustafson P, Mertens F, et al. Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer. 2002;33(2):188–200.
11. Orr LC, Fleitz J, McGavran L, et al. Cytogenetics in pediatric low-grade astrocytomas. Med Pediatr Oncol. 2002;38(3):173–177.
12. Biswas S, Rao CM. Epigenetics in cancer: fundamentals and beyond. Pharmacol Ther. 2017;173:118–134.
13. Chen ZX, Riggs AD. DNA methylation and demethylation in mammals. J Biol Chem. 2011;286(21):18347–18353.
14. Chakravarthi BV, Nepal S, Varambally S. Genomic and epigenomic alterations in cancer. Am J Pathol. 2016;186(7):1724–1735.
15. Weisenberger DJ. Characterizing DNA methylation alterations from The Cancer Genome Atlas. J Clin Invest. 2014;124(1):17–23.
16. Zhao R, Choi BY, Lee MH, et al. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EBioMedicine. 2016;8:30–39.
17. Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015;15:38.
18. Chakraborty C, Sharma AR, Sharma G, et al. The novel strategies for next-generation cancer treatment: miRNA combined with chemotherapeutic agents for the treatment of cancer. Oncotarget. 2018;9(11):10164– 10174.
19. Dizdaroglu M. Oxidatively induced DNA damage and its repair in cancer. Mutat Res Rev Mutat Res. 2015;763:212–245.
20. Feinberg AP, Koldobskiy MA, Gondor A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat Rev Genet. 2016;17(5):284–299.
21. Wallace SS, Murphy DL, Sweasy JB. Base excision repair and cancer. Cancer Lett. 2012;327(1–2):73–89.
22. Kim YJ, Wilson DM, 3rd. Overview of base excision repair biochemistry. Curr Mol Pharmacol. 2012;5(1):3–13.
23. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–413.
24. Li SKH, Martin A. Mismatch repair and colon cancer: mechanisms and therapies explored. Trends Mol Med. 2016;22(4):274–289.
25. Helleday T, Eshtad S, Nik-Zainal S. Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet. 2014;15(9):585–598.
26. Aparicio T, Baer R, Gautier J. DNA double-strand break repair pathway choice and cancer. DNA Repair (Amst). 2014;19:169–175.
27. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Nonhomologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol. 2017;18(8):495–506.
28. Katsanis SH, Katsanis N. Molecular genetic testing and the future of clinical genomics. Nat Rev Genet. 2013;14(6):415–426.
29. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev Cancer. 2004 ; 4(3):177-83.
30. Tokheim CJ, Papadopoulos N, Kinzler KW, et al. Evaluating the evaluation of cancer driver genes. Proc Natl Acad Sci U S A. 2016;113(50):14330-14335..
31. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008; 321(5897):1807-12.
32. Hou AH, Tien HF. Genomic landscape in acute myeloid leukemia and its implications in risk classification and targeted therapies. J Biomed Sci. 202021;27(1):81.
33. Chen G, Cai Z, Dong X, et al. Genomic and Transcriptomic Landscape of Tumor Clonal Evolution in Cholangiocarcinoma. Front Genet. 2020;11:195.
34. Yang H, Ye D, Guan KL, et al. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res. 2012;18(20):5562-71.
35. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424-33.
36. Varela I, Tarpey P, Raine K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011;469(7331):539-42.
37. Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS One. 2013; 8(1):e55119.
38. Kobrinski DA, Yang H, Kittaneh M. BAP1: role in carcinogenesis and clinical implications. Transl Lung Cancer Res. 2020;9(Suppl 1):S60-S66.
39. Li Y, Shi J, Yang J, et al. Uveal melanoma: progress in molecular biology and therapeutics. Ther Adv Med Oncol. 2020 Oct 22;12:1758835920965852.
40. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64-9.
41. Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81-94.
42. Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013;501(7467):338-45.
43. Turner NC, Reis-Filho JS. Genetic heterogeneity and cancer drug resistance. Lancet Oncol. 2012 ;13(4):e178- 85. Mar 30.
44. Venkatesan S, Swanton C, Taylor BS, Costello JF. Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution. Cold Spring Harb Perspect Med. 2017;7(8):a026617.
45. Zhang Y, Ma Y, Li Y, et al. Comparative analysis of cooccurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations. J Cancer Res Clin Oncol. 2019;145(3):747- 757.
46. Ljungman M, Lane DP. Transcription - guarding the genome by sensing DNA damage. Nat Rev Cancer. 2004;4(9):727-37.
47. Perrimon N, Pitsouli C, Shilo BZ. Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb Perspect Biol. 2012;4(8):a005975.
48. Baish JW, Stylianopoulos T, Lanning RM, Kamoun WS, Fukumura D, Munn L et al. Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A. 2011; 108(5):1799-803.
49. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010; 10(2):116-29.
50. Yun J, Rago C, Cheong I, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009; 325(5947):1555-9.
51. Medema RH, Macůrek L. Checkpoint control and cancer. Oncogene. 2012; 31(21):2601-13.
52. Bertier G, Carrot-Zhang J, Ragoussis V, Joly Y. Integrating precision cancer medicine into healthcare—policy, practice, and research challenges. Genome Med. 2016; 8(1):108.
53. Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12(1): 8.
54. McLeod HL. Cancer pharmacogenomics: early promise, but concerted effort needed. Science. 2013; 339(6127):1563-6.
Cómo citar
[1]
Cardona, A.F. et al. 2021. Evolución de la genómica tumoral. Medicina. 42, 4 (feb. 2021), 656–674. DOI:https://doi.org/10.56050/01205498.1566.
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Publicado
2021-02-12
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Perspectiva del diagnóstico y Tratamiento del Cancer
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Derechos de autor 2021 Medicina
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