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Erstad DJ, Cusack JC. Mutational analysis of merkel cell carcinoma. Cancers (Basel). 2014;6(4):2116-36doi: 10.3390/cancers6042116.
Erstad, D. J., & Cusack, J. C. (2014). Mutational analysis of merkel cell carcinoma. Cancers, 6(4), 2116-36. https://doi.org/10.3390/cancers6042116
Erstad, Derek J, and Cusack, James C. "Mutational analysis of merkel cell carcinoma." Cancers vol. 6,4 (2014): 2116-36. doi: https://doi.org/10.3390/cancers6042116
Erstad DJ, Cusack JC. Mutational analysis of merkel cell carcinoma. Cancers (Basel). 2014 Oct 17;6(4):2116-36. doi: 10.3390/cancers6042116. PMID: 25329450; PMCID: PMC4276959.
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Cancers (Basel). 2014 Oct 17;6(4):2116-36. doi: 10.3390/cancers6042116.

Mutational analysis of merkel cell carcinoma.

Cancers

Derek J Erstad, James C Cusack

Affiliations

  1. Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. [email protected].
  2. Division of Surgical Oncology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. [email protected].

PMID: 25329450 PMCID: PMC4276959 DOI: 10.3390/cancers6042116

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy that is associated with a poor prognosis. The pathogenesis of MCC is not well understood, and despite a recent plethora of mutational analyses, we have yet to find a set of signature mutations implicated in the majority of cases. Mutations, including TP53, Retinoblastoma and PIK3CA, have been documented in subsets of patients. Other mechanisms are also likely at play, including infection with the Merkel cell polyomavirus in a subset of patients, dysregulated immune surveillance, epigenetic alterations, aberrant protein expression, posttranslational modifications and microRNAs. In this review, we summarize what is known about MCC genetic mutations and chromosomal abnormalities, and their clinical significance. We also examine aberrant protein function and microRNA expression, and discuss the therapeutic and prognostic implications of these findings. Multiple clinical trials designed to selectively target overexpressed oncogenes in MCC are currently underway, though most are still in early phases. As we accumulate more molecular data on MCC, we will be better able to understand its pathogenic mechanisms, develop libraries of targeted therapies, and define molecular prognostic signatures to enhance our clinicopathologic knowledge.

References

  1. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1545-9 - PubMed
  2. Head Neck. 2010 Mar;32(3):333-40 - PubMed
  3. J Virol. 2013 Dec;87(23):13009-19 - PubMed
  4. J Invest Dermatol. 2013 Oct;133(10):2453-2460 - PubMed
  5. Mod Pathol. 2009 Jul;22(7):959-68 - PubMed
  6. Am J Clin Oncol. 2010 Oct;33(5):495-9 - PubMed
  7. Cancer Genet Cytogenet. 1991 Jul 1;54(1):109-13 - PubMed
  8. Gastroenterology. 2004 Jan;126(1):318-21 - PubMed
  9. Genes Chromosomes Cancer. 1997 Sep;20(1):93-7 - PubMed
  10. J Clin Pathol. 2005 Mar;58(3):297-300 - PubMed
  11. Genes Chromosomes Cancer. 1996 Feb;15(2):102-7 - PubMed
  12. N Engl J Med. 1998 Oct 22;339(17):1247-8 - PubMed
  13. Int J Cancer. 2012 Feb 15;130(4):847-56 - PubMed
  14. Clin Diagn Lab Immunol. 2000 Mar;7(2):326 - PubMed
  15. Anticancer Res. 2005 Mar-Apr;25(2A):853-8 - PubMed
  16. Int J Cancer. 2002 May 20;99(3):352-60 - PubMed
  17. Int J Cancer. 2010 Sep 1;127(6):1493-6 - PubMed
  18. Am J Clin Pathol. 1998 May;109(5):565-70 - PubMed
  19. Head Neck. 2011 Sep;33(9):1294-300 - PubMed
  20. N Engl J Med. 1993 Oct 28;329(18):1318-27 - PubMed
  21. Cell Host Microbe. 2013 Aug 14;14(2):125-35 - PubMed
  22. Cancer Res. 2006 Aug 1;66(15):7401-4 - PubMed
  23. Mod Pathol. 2007 Jan;20(1):90-101 - PubMed
  24. Cancer Genet Cytogenet. 1989 Mar;38(1):43-8 - PubMed
  25. Mod Pathol. 2014 Aug;27(8):1073-87 - PubMed
  26. J Invest Dermatol. 2007 Jul;127(7):1572-3 - PubMed
  27. Arch Pathol Lab Med. 2010 Nov;134(11):1711-6 - PubMed
  28. PLoS Pathog. 2009 Sep;5(9):e1000578 - PubMed
  29. Curr Probl Cancer. 2010 Jan-Feb;34(1):14-37 - PubMed
  30. Int J Cancer. 2011 Aug 1;129(3):619-28 - PubMed
  31. Oncogene. 2013 Jan 17;32(3):277-85 - PubMed
  32. PLoS One. 2013 Nov 18;8(11):e80543 - PubMed
  33. Cancer. 2008 Nov 1;113(9):2549-58 - PubMed
  34. J Invest Dermatol. 2006 May;126(5):1135-42 - PubMed
  35. J Virol. 2013 Aug;87(16):9173-88 - PubMed
  36. Science. 2008 Feb 22;319(5866):1096-100 - PubMed
  37. Cell. 1992 Jun 26;69(7):1237-45 - PubMed
  38. J Clin Oncol. 2011 Apr 20;29(12):1539-46 - PubMed
  39. APMIS. 2014 Dec;122(12):1157-66 - PubMed
  40. Pathol Res Pract. 2011 Aug 15;207(8):463-7 - PubMed
  41. Clin Cancer Res. 2012 Mar 1;18(5):1227-36 - PubMed
  42. J Biol Chem. 2014 Jan 3;289(1):529-39 - PubMed
  43. Am J Clin Pathol. 2013 Dec;140(6):838-44 - PubMed
  44. J Cutan Pathol. 2013 Jul;40(7):623-30 - PubMed
  45. J Cutan Pathol. 2007 Jan;34(1):22-6 - PubMed
  46. Ann Surg Oncol. 2013 Apr;20(4):1365-73 - PubMed
  47. PLoS Pathog. 2010 Aug 26;6(8):e1001076 - PubMed
  48. J Clin Invest. 2011 Sep;121(9):3623-34 - PubMed
  49. J Invest Dermatol. 2008 Jul;128(7):1788-96 - PubMed
  50. J Invest Dermatol. 2009 Jun;129(6):1547-55 - PubMed
  51. Mod Pathol. 2008 Feb;21(2):96-104 - PubMed
  52. J Cutan Pathol. 2000 Mar;27(3):118-20 - PubMed
  53. Br J Cancer. 2006 Feb 27;94(4):455-9 - PubMed
  54. APMIS. 2013 Aug;121(8):755-69 - PubMed
  55. J Clin Oncol. 2011 Apr 20;29(12):1612-9 - PubMed
  56. Ann Surg Oncol. 2012 Oct;19(11):3325-34 - PubMed
  57. J Cutan Pathol. 2008 Feb;35(2):197-202 - PubMed
  58. Cancer Res. 1998 Apr 1;58(7):1503-8 - PubMed
  59. Histopathology. 2000 Nov;37(5):445-51 - PubMed
  60. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1814-9 - PubMed
  61. PLoS One. 2012;7(2):e31255 - PubMed
  62. Eur Arch Otorhinolaryngol. 2011 Nov;268(11):1639-46 - PubMed
  63. Am J Dermatopathol. 2012 Aug;34(6):592-6 - PubMed
  64. Br J Cancer. 2000 Feb;82(4):823-6 - PubMed
  65. J Invest Dermatol. 2014 Feb;134(2):507-517 - PubMed
  66. Int J Cancer. 2002 Sep 10;101(2):137-45 - PubMed
  67. J Virol. 2014 Mar;88(6):3144-60 - PubMed
  68. J Cutan Pathol. 1996 Oct;23(5):391-7 - PubMed
  69. J Virol. 2013 Jun;87(11):6118-26 - PubMed
  70. Arch Dermatol Res. 2003 Aug;295(4):146-54 - PubMed
  71. Virchows Arch. 2008 May;452(5):559-63 - PubMed
  72. Br J Dermatol. 2005 Jul;153(1):229-32 - PubMed
  73. J Skin Cancer. 2014;2014:289548 - PubMed
  74. Clin Cancer Res. 2011 Jul 15;17(14):4806-13 - PubMed
  75. Cancers (Basel). 2013 Feb 28;5(1):234-54 - PubMed
  76. Histopathology. 2005 Jun;46(6):622-34 - PubMed
  77. Cytopathology. 2008 Feb;19(1):48-51 - PubMed
  78. Wien Klin Wochenschr. 2013 Sep;125(17-18):501-7 - PubMed
  79. J Am Acad Dermatol. 1997 Nov;37(5 Pt 1):734-9 - PubMed
  80. J Gastrointest Surg. 2011 Jan;15(1):63-70 - PubMed
  81. J Cutan Pathol. 2007 Apr;34(4):324-9 - PubMed
  82. Ann Oncol. 2011 Feb;22(2):250-6 - PubMed
  83. J Natl Cancer Inst. 2009 Jul 1;101(13):938-45 - PubMed
  84. J Am Acad Dermatol. 2008 Mar;58(3):375-81 - PubMed
  85. Hum Pathol. 2012 Dec;43(12):2282-91 - PubMed
  86. J Invest Dermatol. 2014 May;134(5):1479-1481 - PubMed
  87. Cancer Res. 2010 Nov 1;70(21):8388-97 - PubMed
  88. J Invest Dermatol. 2013 Apr;133(4):936-45 - PubMed
  89. Int J Cancer. 2001 May 1;92(3):409-13 - PubMed
  90. Clin Cancer Res. 2011 Nov 1;17(21):6671-80 - PubMed
  91. Tumour Biol. 2013 Feb;34(1):349-57 - PubMed
  92. Nature. 1992 Jul 2;358(6381):80-3 - PubMed
  93. Hum Pathol. 2010 Oct;41(10):1405-12 - PubMed
  94. Hum Pathol. 2013 Aug;44(8):1656-64 - PubMed
  95. J Skin Cancer. 2012;2012:680410 - PubMed
  96. Mod Pathol. 2011 Nov;24(11):1451-61 - PubMed
  97. Mod Pathol. 2004 May;17(5):561-7 - PubMed
  98. Cell Commun Signal. 2014 Apr 28;12:30 - PubMed
  99. Cancer Genet Cytogenet. 1988 Jul 15;33(2):305-9 - PubMed
  100. J Cutan Pathol. 2010 Jan;37(1):20-7 - PubMed

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