Browsing by Author "Caruana, Kevin"

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    Differential Expression of Telomere DNA in Blood content for Cancer Diagnostics
    (Office of the Vice Chancellor for Research, 2014-04-11) Caruana, Kevin; Tanaka, Hiromi
    Human blood typically contains a very small amount of cell free DNA (cfDNA) of uncertain origin. The amount and makeup of this circulating DNA been shown to change with the presence of cancer in the body. These alterations are used currently in some countries as very rudimentary tests for specific cancers and their mutations, which is reflected in the cfDNA. Little is known about the extent of the changes as the field is very young, though very promising. Telomeres are repetitive DNA elements that function as chromosomal caps, and are essential to cancer survival. Their function in cell life limitation mandates that all cancer find a method by which to bring about telomere dysfunction, making telomere a uniquely universal cancer element. It is possible, therefore, that telomere presence in cfDNA would be altered in many cancers, providing a powerful biomarker for cancer diagnostics and prognostics. This study shows a direct link between cancer presence and an augmented telomeric DNA ration in the blood. This idea could pave the way for a powerful early warning test for difficult cancers.
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    The presence of telomere fusion in sporadic colon cancer independently of disease stage, TP53/KRAS mutation status, mean telomere length, and telomerase activity
    (Elsevier, 2014-10) Tanaka, Hiromi; Beam, Matthew J.; Caruana, Kevin; Medical & Molecular Genetics, School of Medicine
    Defects in telomere maintenance can result in telomere fusions that likely play a causative role in carcinogenesis by promoting genomic instability. However, this proposition remains to be fully understood in human colon carcinogenesis. In the present study, the temporal sequence of telomere dysfunction dynamics was delineated by analyzing telomere fusion, telomere length, telomerase activity, hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18 colon cancer patients. Our results revealed that both the deficiency of p53 and the shortening of mean telomere length were not necessary for producing telomere fusions in colon tissue. In five cases, telomere fusion was observed even in tissue adjacent to cancerous lesions, suggesting that genomic instability is initiated in pathologically non-cancerous lesions. The extent of mean telomere attrition increased with lymph node invasiveness of tumors, implying that mean telomere shortening correlates with colon cancer progression. Telomerase activity was relatively higher in most cancer tissues containing mutation(s) in KRAS or BRAF and/or TP53 compared to those without these hotspot mutations, suggesting that telomerase could become fully active at the late stage of colon cancer development. Interestingly, the majority of telomere fusion junctions in colon cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum, this meticulous correlative study not only highlights the concept that telomere fusion is present in the early stages of cancer regardless of TP53/KRAS mutation status, mean telomere length, and telomerase activity, but also provides additional insights targeting key telomere fusion junctions which may have significant implications for colon cancer diagnoses.