Telomere Maintenance Mechanisms in Cancer.


Author: Gaspar TB1,2,3,4, Sá A5,6,7, Lopes JM8,9,10,11, Sobrinho-Simões M12,13,14,15, Soares P16,17,18, Vinagre J19,20,21

Affiliation: <sup>1</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. tgaspar@ipatimup.pt.

<sup>2</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. tgaspar@ipatimup.pt.

<sup>3</sup>Medical Faculty of University of Porto (FMUP), 4200-139 Porto, Portugal. tgaspar@ipatimup.pt.

<sup>4</sup>Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal. tgaspar@ipatimup.pt.

<sup>5</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. asa@ipatimup.pt.

<sup>6</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. asa@ipatimup.pt.

<sup>7</sup>Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal. asa@ipatimup.pt.

<sup>8</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. jmlopes@ipatimup.pt.

<sup>9</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. jmlopes@ipatimup.pt.

<sup>10</sup>Medical Faculty of University of Porto (FMUP), 4200-139 Porto, Portugal. jmlopes@ipatimup.pt.

<sup>11</sup>Department of Pathology and Oncology, Centro Hospitalar São João, 4200-139 Porto, Portugal. jmlopes@ipatimup.pt.

<sup>12</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. ssimoes@ipatimup.pt.

<sup>13</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. ssimoes@ipatimup.pt.

<sup>14</sup>Medical Faculty of University of Porto (FMUP), 4200-139 Porto, Portugal. ssimoes@ipatimup.pt.

<sup>15</sup>Department of Pathology and Oncology, Centro Hospitalar São João, 4200-139 Porto, Portugal. ssimoes@ipatimup.pt.

<sup>16</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. psoares@ipatimup.pt.

<sup>17</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. psoares@ipatimup.pt.

<sup>18</sup>Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313 Porto, Portugal. psoares@ipatimup.pt.

<sup>19</sup>Cancer Signaling and Metabolism Group, Institute for Research and Innovation in Health Sciences (i3S), University of Porto, 4200-135 Porto, Portugal. jvinagre@ipatimup.pt.

<sup>20</sup>Cancer Signaling and Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), 4200-135 Porto, Portugal. jvinagre@ipatimup.pt.

<sup>21</sup>Medical Faculty of University of Porto (FMUP), 4200-139 Porto, Portugal. jvinagre@ipatimup.pt.
Conference/Journal: Genes (Basel).
Date published: 2018 May 3
Other:
 Volume ID: 9   ,  Issue ID: 5   ,  Special Notes: doi: 10.3390/genes9050241.   ,  Word Count: 220  
    Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the TERT promoter (TERTp), amplification of the genes TERT and TERC, polymorphic variants of the TERT gene and of its promoter, rearrangements of the TERT gene, epigenetic changes, ALT, and non-defined TMM (NDTMM). We gathered information from over fifty thousand patients reported in 288 papers in the last years. This wide data collection enabled us to portray, by organ/system and histotypes, the prevalence of TERTp mutations, TERT and TERC amplifications, and ALT in human tumours. Based on this information, we discuss the putative future clinical impact of the aforementioned mechanisms on the malignant transformation process in different setups, and provide insights for screening, prognosis, and patient management stratification.



KEYWORDS: TERC; TERT; alternative lengthening of telomeres (ALT); cancer; non-defined telomere maintenance mechanism (NDTMM); promoter; telomerase; telomere; telomere maintenance mechanism (TMM)



PMID: 29751586  DOI: 10.3390/genes9050241