Table 1.
Prevalence and distribution of telomerase reverse transcriptase promoter (TERTp) mutations in cancer genomes. The prevalence of TERTp mutations is given as percentage and as total number of cases.
| Cancer Type | Stage | Prevalence of Mutations | −146 C>T | −124 C>T | Tert Upregulation | Methods | Sample Origin | Remarks | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Central nervous system (CNS) | |||||||||
| GBM | 62% 24/39 |
25% 6/24 |
75% 18/24 |
Yes | DNA sequencing, qRT-PCR, IHC, |
Patients (Portugal) |
Associated with older age. | [52] | |
| GBM | IV | 83.9% 47/55 |
34% 16/47 |
65.9% 31/47 |
Yes | DNA sequencing, qRT-PCR, TRAP, reporter assays |
Patients (China) |
Associated with older age. | [57] |
| GBM (Primary) | IV | 83% 65/78 |
24.6% 16/65 |
75.4% 49/65 |
N/A | DNA sequencing | Patients (US American) |
Associated with shorter OS, IDH-wt, ATRX-wt, exclusively in EGFRmut samples. |
[77] |
| GBM | I–IV | 44.6% 45/101 |
26.7% 12/45 |
73.3% 33/45 |
Yes | DNA sequencing, qRT-PCR, reporter assays |
Patients (China) |
Associated with late-stage disease and patient age. Only in gliomas, not in pituitary adenocarcinomas, meningiomas or secondary metastases. |
[60] |
| GBM | 55% 197/358 |
27% 54/197 |
73% 144/197 |
N/A | DNA sequencing | Patients (Switzerland) |
Associated with shorter OS and with EGFRmut. Negatively associated with mutant IDH and TP53. More frequent in primary (58%) than in secondary GBM (28%). One patient with both −146 C>T + −124 C>T mutation. |
[111] | |
| GBM (primary & secondary) |
IV | 80.3% 143/178 |
* | * | N/A | DNA sequencing | Patients | Associated with shorter OS in patients without rs2853669 TERT
-245 A>G polymorphism. Detected in 4/14 (28%) secondary GBM. |
[81] |
| GBM | IV | 66.9% 141/211 |
25.5% 36/141 |
74.5% 105/141 |
N/A | DNA sequencing | Patients (Portugal & Brazil) | Associated with older age, poor prognosis, and shorter survival. Reversed by rs2853669 TERT −245 A>G polymorphism. |
[85] |
| GBM | 60.4% 29/48 |
24.1% 7/29 |
75.8% 22/29 |
Yes | DNA sequencing, qRT-PCR |
Patients (Korea) | Associated with older age. Not associated with OS or DFS. Associated with MGMT methylation and EGFR amplification. Associated with rs2853669 TERT −245 A>G polymorphism (21/29 patients). rs2853669 TERT −245 A>G polymorphism reversed TERT upregulation by TERTp mutations. |
[64] | |
| GBM | 73% 92/126 |
28% 26/92 |
82% 66/92 |
Yes | DNA sequencing, qRT-PCR, TRAP, qPCR |
Mutually exclusive with IDH-1 mutations. Associated with shorter telomeres. Associated with lower OS in IDH-1wt patients. rs2853669 TERT -245 A>G polymorphism associated with improved OS in patients without TERTp mutations, and with worse OS in patients with TERTp mutations. |
[65] | ||
| GBM (primary) | 86% 79/92 |
25% 20/79 |
75% 69/79 |
DNA sequencing | Associated with older age and shorter OS. Homozygous rs2853669 TERT −245 A>G polymorphism associated with worse OS in patients without and with TERTp mutations. |
[84] | |||
| GBM and gliomas (primary) | 100% 10/10 |
10% 1/10 |
90% 9/10 |
N/A | DNA sequencing | Patients | In primary GBM, characterized by 10q deletion EFGR amplification. | [58] | |
| GBM | 94% 33/35 |
36% 12/33 |
64% 21/33 |
2.2–286-fold compared to normal astrocytes | DNA sequencing, qRT-PCR |
Cell lines | [58] | ||
| Total GBM | 905/1331 (68%) |
206/762 (27%) |
567/762 (73%) |
||||||
| Oligodendroglioma | II | 45% 10/22 |
20% 2/10 |
80% 8/10 |
Yes | DNA sequencing, qRT-PCR, IHC |
Patients (Portugal) |
[52] | |
| Oligodendroglioma | II–III | 70% 7/10 |
14.3% 1/7 |
85.7% 6/7 |
Yes | DNA sequencing, qRT-PCR, TRAP, Reporter Assays |
Patients (China) |
Associated with older age. | [57] |
| Oligodendroglioma | II–III | 46.3% 25/54 |
24% 6/25 |
76% 19/25 |
N/A | DNA sequencing | Patients (Portugal & Brazil) |
Associated with older age at diagnosis. Not associated with lower survival. |
[85] |
| Oligodendroglioma | 73.5% 25/34 |
20% 5/25 |
80% 20/25 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) |
Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1mut if not total loss of 1p19q. |
[53] | |
| Oligodendroglioma | II–IV | 66.81% 151/226 |
* | * | N/A | DNA sequencing | Patients (US American) |
Associated with shorter OS. Can be associated with ATRX mutations or IDHmut/1p19q loss. |
[80] |
| Oligodendroglioma | II–III | 63.2% 12/19 |
41.7% 5/12 |
58.3% 7/12 |
N/A | DNA sequencing | Patients (US American) |
IDH-wt only. Associated with worse prognosis in IDH-wt. Associated with older age. Mutually exclusive with ATRX mutations. |
[77] |
| Anaplastic oligodendroglioma |
III | 54% 13/24 |
30.8% 4/13 |
69.2% 9/13 |
Yes | DNA sequencing, qRT-PCR, IHC, |
Patients (Portugal) |
Associated with older age. | [52] |
| Anaplastic oligodendroglioma |
74.2% 23/31 |
30.4% 7/23 |
69.6% 16/23 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) |
Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1 if not total loss of 1p19q. |
[53] | |
| Anaplastic oligodendroglioma |
III | 88.5% 23/26 |
43.5% 10/23 |
56.5% 13/23 |
N/A | DNA sequencing | Patients (US American) |
Associated with older age. IDH-wt only. Associated with worse prognosis in IDH-wt. Mutually exclusive with ATRX mutations. |
[77] |
| Total Oligodendroglioma |
289/446 (64.7%) |
40/138 (29%) |
98/138 (71%) |
||||||
| Diffuse astrocytomas | 19.2% 10/52 |
20% 2/10 |
80% 8/10 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) |
Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1 if not total loss of 1p19q. |
[53] | |
| Diffuse astrocytoma | II | 15% 3/20 |
33,3% 1/3 |
66,6% 2/3 |
Yes | DNA sequencing, qRT-PCR, IHC |
Patients (Portugal) |
Associated with older age. | [52] |
| Diffuse astrocytoma | II | 20% 8/40 |
25% 2/8 |
62.5% 5/8 |
Yes | DNA sequencing, qRT-PCR, TRAP, reporter assays |
Patients (China) |
Associated with age. | [57] |
| Diffuse astrocytoma | II | 15.2% 7/46 |
16.7% 1/7 |
83.3% 6/7 |
N/A | DNA sequencing | Patients (Portugal & Brazil) |
Frequency increased with grade. | [85] |
| Total Diffuse Astrocytoma | 28/158 (17.7%) |
6/28 (21.4%) |
21/28 (75%) |
||||||
| Astocytoma | II–IV | 62.5% 416/665 |
N/A | N/A | N/A | DNA sequencing | Patients (US American) |
Associated with shorter OS. Can be associated with ATRX mutations or IDHmut/1p1q loss. |
[80] |
| Anaplastic Astrocytomas | III | 10% 1/10 |
0% 0/1 |
100% 1/1 |
N/A | DNA sequencing | Patients (Portugal & Brazil) |
Frequency increased with grade. | [85] |
| Anaplastic Astrocytoma | III | 33.3% 4/12 |
0% 0/4 |
100% 4/4 |
Yes | DNA sequencing, qRT-PCR, TRAP, reporter assays |
Patients (China) |
Correlation with age. | [57] |
| Anaplastic Astrocytomas | III | 25.3% 20/79 |
20% 4/20 |
80% 16/20 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) |
Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1 if not total loss of 1p19q. | [53] |
| Total Anaplastic Astrocytomas | 25/101 (24.7%) |
4/25 (16%) |
21/25 (84%) |
||||||
| Mixed Oligoastocytoma | II–IV | 32.3% 63/195 |
* | * | N/A | DNA sequencing | Patients (US American) |
Associated with shorter OS. Can be associated with ATRX mutations or IDHmut/1p1q loss. |
[80] |
| Oligoastrocytoma | 40% 14/35 |
28.6% 4/14 |
71.4% 10/14 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) |
Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1 if not total loss of 1p19q. | [53] | |
| Oligoastrocytoma | II–III | 40.0% 4/10 |
50% 2/4 |
50% 2/4 |
N/A | DNA sequencing | Patients (Portugal & Brazil) |
Not associated with lower survival. | [85] |
| Anaplastic Oligoastrocytoma | 48.9% 22/45 |
27.3% 6/22 |
72.7% 16/22 |
Yes | DNA sequencing, qRT-PCR |
Patients (Japan) | Associated with total 1p19q loss and IDH-1/2 mutations (98%) but exclusive with IDH-1 if not total loss of 1p19q. | [53] | |
| Total Oligoastrocytoma |
103/285 (36.1%) |
12/40 (30%) |
28/40 (70%) |
||||||
| Medulloblastoma | 33.3% 2/6 |
50% 1/2 |
50% 1/2 |
N/A | DNA sequencing | Patients (China) | Associated with age. | [57] | |
| Medulloblastoma | 20.9% 19/91 |
0%0/19 | 100% 19/19 |
N/A | DNA sequencing | Patients (US American) |
IDH-wt and ATRX-wt only. Associated with worse prognosis in IDH-1-wt. Associated with older age. Mutually exclusive with ALT. |
[77] | |
| Total Medulloblastoma |
21/97 (21.6%) |
1/21 (4.7%) |
20/21 (95.3%) |
||||||
| Skin | |||||||||
| Melanoma | 71% 50/70 |
46% 23/50 |
54% 27/50 |
Yes | DNA sequencing, reporter vectors |
Patients & cell lines |
[50] | ||
| Melanoma | 32.5% 25/77 |
20% 5/25 |
28% 7/25 |
N/A | DNA sequencing | Patients | -57 C>T germline mutation in family with history of melanoma. High prevalence in metastatic cell lines (85%) compared to primary melanoma (32.5%). CC>TT −139/−138 tandem mutation in 10.4% patients. Concomitant with BRAF mutations in 47% of cases. |
[49] | |
| Melanoma | 29% 16/56 |
50% 8/16 |
50% 8/16 |
N/A | DNA sequencing | Patients (Portugal) |
Associated with BRAF mutations. | [52] | |
| Melanoma | 34% 97/287 |
52.5% 51/97 |
36% 35/97 |
Yes | DNA sequencing, qRT-PCR |
Patients (Spain) |
CC>TT −139/−138 tandem mutations in 4/97 (4.1%) patients. Associated with BRAF mutations in 50% cases. |
[88] | |
| Melanoma | 41.6% 121/291 |
* | * | N/A | DNA sequencing | Patients (Spain) | Associated with shorter telomeres in tumor and with accelerated telomere shortening rate. Associated with BRAF/NRAS mutation in 75/243 cases. Telomere shortening rate: BRAF/NRASmut+TERTpmut>TERTpmut>BRAF/NRASmut |
[115] | |
| Melanoma | 22% 26/116 |
35% 9/26 |
46% 12/26 |
Yes | DNA sequencing, IHC |
Patients (Portugal) |
Associated with reduced OS & DFS. More prevalent in sun-exposed regions. Associated with increased mitotic rates. −138/−138 CC>TT tandem mutation in 2/26 (7.7%) patients. −125/−124 CC>TT tandem mutation in 3/26 (11.5%) patients. Associated with BRAF-V600E mutation (58% of cases). |
[89] | |
| Melanoma | 38.6% 116/300 |
50% 58/116 |
32.8% 32/116 |
N/A | DNA sequencing | Patients (Spain) | Associated with shorter OS and DFS. −139/−138 CC>TT & −125/−124 CC>TT tandem mutations in 16/116 cases (13.8%). Associated with BRAF/NRAS mutations in 126/283 (44.5%) cases. Reversed by rs2853669 TERT -245 A>G polymorphism. |
[116] | |
| Melanoma | 54.8% 63/115 |
61.9% 39/63 |
30.2% 19/63 |
N/A | DNA sequencing | Patients (Austria) | −139/−138 CC>TT tandem mutations in 4/63 (6.3%) patients. −125/−124 CC>TT tandem mutation in 1/63 (1.6%) patient. Associated with BRAF/NRAS mutation in 75/243 cases. Associated with rs2853669 TERT -245 A>G polymorphism. |
[91] | |
| Total Melanoma | 514/1312 (39.2%) |
193/398 (48.5%) |
140/398 (35.1%) |
||||||
| Basal cell carcinoma | 55.6% 18/32 |
55.6% 10/18 |
22.2% 4/18 |
N/A | DNA sequencing | Patients (Germany) | [55] | ||
| Basal cell carcinoma (sporadic & nevoid) |
74% 31/42 |
35.5% 11/31 |
45.1% 14/31 |
N/A | DNA sequencing | Patients | Mostly homozygous. −139/−138 CC>TT tandem mutation in 7/31 (22.6%) patients. −125/−124 CC–TT tandem mutation in 5/31 (16.1%) patients. 1 patient with −139/−138 CC>TT + −125/−124 CC>TT tandem mutations. Mutations more frequent in basal cell carcinoma than in squamous cell carcinoma. |
[90] | |
| Basal cell carcinoma | 38.7% 76/196 |
43% 33/76 |
49% 37/76 |
no | DNA sequencing, IHC |
Patients (Portugal) |
No correlation with clinical parameters. Higher prevalence in patients not exposed to X-irradiation: 48/94 (51%) vs. 28/102 (27%) in X-irradiated patients. −124 C>T more frequent than −146 C>T in non-X-irradiated patients; −146 C>T more frequent in X-irradiated patients. −139/138 CC>TT tandem mutation in 2/76 (2.6%) patients, 2 patients with −146 C>T + −124 C>T mutations. |
[89] | |
| Total Basal cell carcinoma | 125/270 (46.2%) |
54/125 (43.2%) |
55/125 (44%) |
||||||
| Cutaneous SCC | 50% 17/34 |
29.4% 5/17 |
29.4% 5/17 |
N/A | DNA sequencing | Patients (Germany) | [55] | ||
| Cutaneous SCC | 50% 13/26 |
54% 7/13 |
31% 4/13 |
N/A | DNA sequencing | Patients | Mostly homozygous. −139/−138 CC>TT tandem mutation in 2/13 (15.4) patients. Mutations more frequent in basal cell carcinoma than in squamous cell carcinoma. |
[90] | |
| Total Cutaneous SCC | 30/60 (50%) |
12/30 (40%) |
9/30 (30%) |
||||||
| Bladder/urinary tract cancers | |||||||||
| Bladder Cancer | 85% 44/52 |
4.5% 2/44 |
95.5% 42/44 |
N/A | DNA sequencing | Patients (China) | [78] | ||
| Urothelial bladder carcinoma | III | 80% 12/15 |
17% 2/12 |
83% 10/12 |
N/A | DNA sequencing | Patients (US American) |
[93] | |
| Urothelial bladder carcinoma | 66.7% 14/21 |
28.6% 4/14 |
71.4% 10/14 |
N/A | DNA sequencing | Patients (US American) |
[77] | ||
| Urothelial bladder carcinoma | 61.7% 148/240 |
25% 37/148 |
58.8% 87/148 |
N/A | DNA sequencing | Patients (China) | Not associated with age. | [57] | |
| Urothelial bladder carcinoma | 59% 48/82 |
37.5% 18/48 |
62.5% 30/48 |
N/A | DNA sequencing, qRT-PCR | Patients (Portugal) | Not associated with age. Low-grade bladder cancer: 67%, high-grade bladder cancer: 56%. |
[52] | |
| Urothelial bladder carcinoma | 65.4% 214/327 |
17.8% 38/214 |
81.8% 175/214 |
N/A | DNA sequencing, relative telomere length | Patients (Sweden) | Associated with shorter telomeres and worse OS. Associated with FGFR3 mutation in 45% of tumors. FGFR3 mutations found in low-grade tumors, TERTp mutations in low-grade and high-grade tumors. Reversed by rs2853669 TERT −245 A>G polymorphism. |
[61] | |
| Urothelial bladder carcinoma | 77.1% 361/468 |
17% 62/361 |
83% 299/361 |
Not increased | DNA sequencing, qRT-PCR | Patients | Not associated with OS, DFS, or clinical outcome. Associated with FGFR3mut. |
[94] | |
| Urothelial bladder carcinoma | 100% 33/33 |
12% 5/33 |
85% 28/33 |
N/A | DNA sequencing | Patients | Pure micropapillary carcinoma and urothelial cancer with focal micropapillary features. | [92] | |
| Urothelial upper tract urinary carcinoma | 76.9% 40/52 |
12.5% 5/40 |
72.5% 29/40 |
N/A | DNA sequencing | Patients (China) |
Not associated with age. | [57] | |
| Urothelial upper tract urinary carcinoma | 47.4% 9/19 |
11.1% 1/9 |
88.9% 8/9 |
N/A | DNA sequencing | Patients (US American) |
[77] | ||
| Urothelial upper tract urinary carcinoma | 29.5% 65/220 |
18.5% 12/65 |
81.5% 53/65 |
N/A | DNA sequencing, Detection in urine |
Patients (China) | Associated with distant metastases. | [118] | |
| Total Urothelial bladder & upper tract urinary carcinoma | 988/1529 (64.6%) |
186/988 (18.8%) |
771/988 (78%) |
||||||
| Thyroid | |||||||||
| Differentiated thyroid cancer | 12.2% 41/336 |
4.9% 2/41 |
95.1% 39/41 |
N/A | DNA sequencing | Patients | Only in malignant lesions. | [108] | |
| Papillary thyroid cancer | 8% 13/169 |
7.7% 1/13 |
84.6% 11/13 |
Yes | DNA sequencing, qRT-PCR, IHC |
Patients (Portugal) |
[52] | ||
| Papillary thyroid cancer | III/IV | 11.3% 46/408 |
15.2% 7/46 |
85.8% 39/46 |
N/A | DNA sequencing | Patients (China) | Associated with older age, larger tumor size, extrathyroid invasion, advanced clinical stage. Associated with BRAF-V600E mutation. |
[99] |
| Papillary thyroid cancer | 27% 13/51 |
7.7% 1/13 |
92.3% 12/13 |
N/A | DNA sequencing | Patients (Sweden) | Only in patients >45. Correlated with shorter telomeres and distal metastases. PTC: 27% (25/332); FTC: 22% (12/70); ATC: 50% (12/36). |
[98] | |
| Papillary thyroid cancer | III/IV | 4.1% 18/432 |
* | * | N/A | DNA sequencing | Patients (Korea) | Associated with BRAF/RAS mutations. Associated with tumor size, stage III-IV, recurrence, decreased OS and DFS with BRAF/RAS mutations: RAS/BRAF >TERTp > RAS/BRAF+TERTp. |
[106] |
| Papillary thyroid cancer | 11.7% 30/257 |
0% 0/30 |
100% 30/30 |
N/A | DNA sequencing | Patients | Only in malignant lesions. −124 C>T associated with BRAF-V600E mutation. |
[108] | |
| Papillary thyroid cancer | 37.7% 10/27 |
10% 1/10 |
90% 9/10 |
N/A | DNA sequencing | Patients (Korea) | No TERTp mutation found in 192 well differentiated cancers without distant metastasis. | [105] | |
| Papillary thyroid cancer | 22% 18/80 |
44% 8/18 |
66% 10/18 |
N/A | DNA sequencing | Patients (US & Japan) |
More frequent in BRAF-wt patients than in BRAFmut. | [100] | |
| Papillary thyroid cancer | 31.8% 77/242 |
0% 0/77 |
100% 77/77 |
N/A | DNA sequencing | Patients (US) |
Associated with older age (>45 years), larger tumor size, stage III–IV, distant metastases, decreased OS and DFS. rs2853669 TERT −245 A>G polymorphism (46.7% (113/242)of patients) increases OS & DFS in patients without TERTp mutations and with BRAF-V600E. |
[103] | |
| Papillary thyroid cancer | 12% 22/182 |
14.6% 3/22 |
86.4% 19/22 |
Yes | DNA sequencing, WB, and IHC |
Patients (Italy) |
Associated with older age and poor prognosis. Increased cytoplasmic localization of TERT. No impact of rs2853669 TERT -245 A>G polymorphism on outcome. |
[102] | |
| Total Papillary thyroid cancer | 247/1848 (13.4%) |
21/229 (9.2%) |
207/229 (90.4%) |
||||||
| Follicular Thyroid Cancer | 13.9% 11/79 |
18.2% 2/11 |
81.8% 9/11 |
N/A | DNA sequencing | Patients | Only in malignant lesions. | [108] | |
| Follicular Thyroid Cancer | 66.7% 2/3 |
50% 1/2 |
50% 1/2 |
N/A | DNA sequencing | Patients (Korea) | No TERTp mutation found in 192 well-differentiated cancers without distanst metastasis. | [105] | |
| Follicular thyroid Cancer | 14% 9/64 |
22.2% 2/9 |
77.8% 7/9 |
Yes | DNA sequencing, qRT-PCR, IHC |
Patients (Portugal) | [52] | ||
| Follicular thyroid cancer | 22% 8/36 |
12.5% 1/8 |
87.5% 7/8 |
N/A | DNA sequencing | Patients (Sweden) | Increased prevalence in ATC: PTC: 27% (25/332); FTC: 22% (12/70); ATC: 50% (12/36). | [98] | |
| Follicular thyroid cancer | 36.4% 8/22 |
12.5% 1/8 |
87.5% 7/8 |
N/A | DNA sequencing | Patients (China) | Associated with older age, larger tumor size, extrathyroid invasion, advanced clinical stage. Associated with BRAF-V600E mutation. |
[99] | |
| Follicular thyroid cancer | III/IV | 5.9% 7/119 |
* | * | N/A | DNA sequencing | Patients (Korea) | Associated with BRAF/RAS mutations. Associated with tumor size, stage III-IV, recurrence, decreased OS and DFS with BRAF/RAS mutations: RAS/BRAF >TERTp > RAS/BRAF+TERTp. |
[106] |
| Follicular thyroid cancer | 14% 8/58 |
38.5% 3/8 |
62.5% 5/8 |
Yes | DNA sequencing, WB, and IHC |
Patients (Italy) | Associated with older age and poor prognosis. Increased cytoplasmic TERT. No impact of rs2853669 TERT -245 A>G polymorphism on outcome. |
[102] | |
| Total Follicular thyroid cancer | 53/381 (13.9%) |
10/46 (21.7%) |
36/46 (78.2%) |
||||||
| Poorly differentiated thyroid cancer | 21% 3/14 |
33.3 1/3 |
66.7 2/3 |
Yes | DNA sequencing, qRT-PCR, IHC |
Patients (Portugal) | [52] | ||
| Poorly differentiated thyroid cancer | 37.5% 3/8 |
0% 0/3 |
100% 3/3 |
N/A | DNA sequencing | Patients | Only in malignant lesions. | [108] | |
| Poorly differentiated thyroid cancer | 29% 2/7 |
50% 1/2 |
50% 1/2 |
N/A | DNA sequencing | Patients (Korea) | No TERTp mutation found in 192 well-differentiated cancers without distanst metastasis. | [105] | |
| Poorly differentiated thyroid cancer | 51.7% 30/58 |
40% 12/30 |
60% 18/30 |
N/A | DNA sequencing | Patients (US & Japan) |
More prevalent in advanced cancer patients with BRAF/RASmut. | [100] | |
| Total Poorly differentiated thyroid cancer | 38/87 (43.7%) |
14/38 (36.8%) |
24/38 (63.2%) |
||||||
| Anaplastic thyroid cancer | 46.3% 25/54 |
8% 2/25 |
92% 23/25 |
N/A | DNA sequencing | Patients | Only in malignant lesions. | [108] | |
| Anaplastic thyroid cancer | 13% 2/16 |
50% 1/2 |
50% 1/2 |
Yes | DNA sequencing, qRT-PCR | Patients (Portugal) | [52] | ||
| Anaplastic thyroid cancer | 50% 10/20 |
0% 0/10 |
100% 10/10 |
N/A | DNA sequencing | Patients (US & Japan) |
More prevalent in advanced cancer patients with BRAF/RASmut. | [100] | |
| Anaplastic thyroid cancer | 50% 10/20 |
20% 2/10 |
80% 8/10 |
N/A | DNA sequencing | Patients (Sweden) | PTC: 27% (25/332); FTC: 22% (12/70); ATC: 50% (12/36). | [98] | |
| Anaplastic thyorid cancer | 33.3% 12/36 |
* | * | N/A | DNA sequencing | Patients (Portugal & Spain) |
Associated with older age, larger tumor size, distant metastases and disease-related death in FTC. PTC: 7.5% (25/332); FTC: 17.1% (12/70); PDTC: 29% (9/31); ATC: 33.4% (12/36). PTC associated with BRAF-V600E mutation in 60.3% of cases. |
[101] | |
| Anaplastic thyroid cancer | 38.7% 41/106 |
10% 4/41 |
90% 37/41 |
N/A | DNA sequencing | Patients (US & China) |
Associated with older age and distal metastases. −124 C>T found in 56.3% of BRAF-V600E mutated cases. |
[104] | |
| Total anaplastic thyroid cancer | 100/252 (39.7%) |
9/88 (10.2%) |
79/88 (89.7%) |
||||||
| Thyroid Cancer cell lines | 91.7% 11/12 |
27.3% 3/11 |
72.7% 8/11 |
N/A | DNA sequencing | Cell lines | [108] | ||
| Thyroid Cancer cell lines | 75% 6/8 |
17.7% 1/6 |
83.3% 5/6 |
N/A | DNA sequencing | ATC cell lines | [98] | ||
| Liver-Hepatocellular Carcinoma (HCC) | |||||||||
| HCC | 31.4% 11/35 |
18,2% 2/11 |
81,8% 9/11 |
N/A | DNA sequencing | Patients (China) | [57] | ||
| HCC | 34% 15/44 |
33.3% 5/15 |
66.7% 10/15 |
N/A | DNA sequencing | Patients (Africa, Asia, Europe) |
Higher TERTp mutation prevalence in African (53%) compared to non-African (24%) populations. | [97] | |
| HCC | 44.3% 27/61 |
3.7% 1/27 |
96.3% 26/27 |
N/A | DNA sequencing | Patients (US American) |
Detected in both HBV-associated and HBV-independent HCC Frequent in HCV-associated HCC. |
[77] | |
| HCC | 48.5% 65/131 |
3.1% 2/65 |
96.9% 63/65 |
N/A | DNA sequencing | Patients (Italy) | 41% of mutations in HBV-associated HCC. 53.6% mutations in HCV-associated HCC. All heterozygous. No −57 A>C. |
[95] | |
| HCC | 31% 85/275 |
1.1% 1/85 |
98.9% 84/85 |
Yes | DNA sequencing, IHC | Patients (China) | HBV-associated HCC. Correlated with age, not with HBV status. Found in 4/7 preneoplastic lesions (HBV-associated HCC). |
[63] | |
| HCC | 65.4% 68/104 |
3% 2/68 |
97% 66/68 |
Yes | DNA sequencing | Patients (Japan) | Associated with older age. Associated with shorter OS and DFS. Associated with HCV infection and excluded from HBV+ HCC. |
[122] | |
| HCC | 58.6% 179/305 |
6.1% 11/179 |
92.7% 166/179 |
Yes 2–10-fold |
DNA sequencing, qRT-PCR | Patients (French) | Detected in cirrhotic preneoplastic macronodules (25%) and cirrhotic adenomas (44%), at last step of malignant transformation into HCC. Absent from HBV-associated tumors 2/179 (1%) −146 C>T. |
[62] | |
| HCC | 29.3% 57/195 |
5.3% 3/57 |
94.7% 54/57 |
No | DNA sequencing, qRT-PCR | Associated with older age. No impact on overall survival. Excluded from HBV-associated HCC. Higher frequency in HCV-associated HCC. |
[96] | ||
| HCC | 54% 254/469 |
4.3% 11/254 |
93% 236/254 |
N/A | DNA sequencing | Patients (Japan, US-European ancestry) | −57 A>C mutation detected in 1.6%. Present in 37% HBV-associated HCC but mutually exclusive with HBV sequence integration. Mutually exclusive with TERT CNV and ATRX mutations. Associated with HCV infection (64% or TERTp mutations). Associated with Wnt pathway mutations. |
[121] | |
| HCC | 60% 9/15 |
11.1% 1/9 |
88.9% 8/9 |
N/A | DNA sequencing | Cell lines | [97] | ||
| Total HCC | 770/1634 (47.1%) |
39/770 (5%) |
722/770 (93.7%) |
||||||
| Cervical | |||||||||
| Cervical SCC | 21.8% 22/101 |
31.8% 7/22 |
45.5% 10/22 |
Yes | qRT-PCR | Patients (Italian women) | [37] | ||
| Cervical SCC | 21.4% 30/140 |
26.7% 8/30 |
73.3% 22/30 |
N/A | DNA sequencing, Association with clinical status | Patients (Indian women) | 75% TERTp mutations in HPV-negative samples. −124 C>T 6/22 were TT homozygous. −146 C>T 2/8 were TT homozygous. |
[36] | |
| Cervical SCC | 4.5% 1/22 |
100% 1/1 |
0% 0/1 |
N/A | DNA sequencing | Patients (US American) |
1 patient with −125 C>A mutation. | ||
| Total Cervical SCC | 53/263 (20.1%) |
16/53 (30.2%) |
32/53 (60.4%) |
[77] | |||||
| Head and Neck Squamous Cell Carcinoma (HNSCC) | |||||||||
| HNSCC | 31.7% 13/41 |
30.8% 4/13 |
69.2% 9/13 |
N/A | DNA sequencing | Patients (Indian women) | Association with clinical status. | [36] | |
| HNSCC | 17% 12/70 |
16.7% 2/12 |
83.3% 10/12 |
N/A | DNA sequencing | Patients (US American) |
11/12 HNSCC with TERTp mutations were in the oral tongue, and 11/23 (47.8%) of HNSCC of the oral tongue harbored TERTp mutations. | [77] | |
| Total HNSCC | 25/111 (22.5%) |
6/25 (24%) |
19/25 (76%) |
||||||
| Ovarian cancer | |||||||||
| Ovarian clear cell carcinoma | 15% 3/20 |
0% 0/3 |
10% 2/3 |
N/A | DNA sequencing | Patients (US American) |
1 patient with −124 C>A mutation. | [77] | |
| Ovarian clear cell carcinoma | 16.5% 37/233 |
8.1% 3/37 |
91.9% 34/37 |
N/A | DNA sequencing, IHC, telomere length evaluation |
Patients | No link with survival or age. TERTp mutations tended to be mutually exclusive with loss of ARID1A protein expression and PIK3CA mutation. |
[132] | |
| Ovarian clear cell carcinoma | 30% 3/10 |
0% 0/3 |
100% 3/3 |
Yes | qRT-PCR | Cell lines | [132] | ||
| Total ovarian clear cell carcinoma | 43/263 (16.3%) |
3/43 (6.9%) |
39/43 (90.7%) |
||||||
N/A: not assessed; *: data not available. TERT: telomerase reverse transcriptase; GBM: glioblastoma multiforme; SCC: squamous cell carcinoma; HNSCC: head and neck squamous cell carcinoma; HCC: hepatocellular carcinoma; GI: gastrointestinal; UC: urothelial cancer; MPC: micropapillary carcinoma; HPV: Human papilloma virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PTC: papillary thyroid cancer; FTC: follicular thyroid cancer; ATC: anaplastic thyroid cancer.