Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: [London] : BioMed Central, c2002-
    • الموضوع:
      Colonic Neoplasms/*genetics ; Colonic Neoplasms/*metabolism ; Mutation/*genetics ; Rectal Neoplasms/*genetics ; Rectal Neoplasms/*metabolism; Carcinogenesis/genetics ; Humans ; Proteogenomics/methods
    • نبذة مختصرة :
      Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.
    • References:
      N Engl J Med. 2016 Sep 22;375(12):1109-12. (PMID: 27653561)
      Science. 2013 Mar 29;339(6127):1546-58. (PMID: 23539594)
      Sci Transl Med. 2016 Oct 19;8(361):361ra140. (PMID: 27798265)
      Cancer Discov. 2012 Feb;2(2):117-21. (PMID: 22585856)
      Hum Mol Genet. 1992 Jul;1(4):229-33. (PMID: 1338904)
      Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
      Mol Cancer Res. 2018 Mar;16(3):476-485. (PMID: 29187560)
      Nat Methods. 2013 Nov;10(11):1046-7. (PMID: 24037243)
      Cancer Cell. 2018 Jan 8;33(1):125-136.e3. (PMID: 29316426)
    • Grant Information:
      I01 BX000545 United States BX BLRD VA
    • Contributed Indexing:
      Keywords: Clonal evolution; Hotspot mutations; Left-sided colon cancer; Proteomics; Rectal cancers; Right-sided colon cancer
    • الموضوع:
      Date Created: 20181223 Date Completed: 20190604 Latest Revision: 20200309
    • الموضوع:
      20240628
    • الرقم المعرف:
      PMC6303985
    • الرقم المعرف:
      10.1186/s12943-018-0923-9
    • الرقم المعرف:
      30577807