Table 5.
Somatic mutations found in ATCs
| Gene | Localization | Gene function | Mutation | Defect in cancer | Physiological effect | Literature |
|---|---|---|---|---|---|---|
| Chromosomal Abberation | ||||||
| KAZN-CIORF196 | 1p36.21, 1p36.21 | N/A | Gene fusion | potential role in progression and development of tumors | Le Pennec et al., 2015 | |
| Gene | ||||||
| ARID1A, ARID1B, ARD2, ARID5B, SMARCB1, PBRM1, ATRX | 1p36.11, 6q25.3, N/A, N/A, 22q11.23, 3p21.1, Xq21.1 | components of the SWI/SNF complex, responsible for the chromatin remodeling | N/A | mutation in one of the complex components leads to dysfunction of the whole complex | N/A | Landa et al., 2016, Latteyer et al., 2016 |
| ALK | 2p23.1 | anaplastic lymphoma kinase | D1203H | hallmark of anaplastic tumors | N/A | Bonhomme et al., 2017, Latteyer et al., 2016 |
| ATM | 11q22.3 | cell-cycle checkpoint, response to DNA damage | E2039K | higher mutation burden, consistent with the lack of checkpoint function | N/A | Landa et al.,2016, Kunstman et al.,2015 |
| BRAF rs113488022 | 7q34 | serine/threonine kinase, response to cell growth factors | V600E | constitutive activation of MAPK pathway | N/A | Santarpia et al., 2008, Guerra et al., 2013, Kasaian et al., 2015, Landa et al., 2016, Latteyer et al., 2016 |
| DAXX | 6p21.32 | transcription repressor binding the sumoylated transcription factors | S641X | potential driver mutation | correlates with non-thyroidal malignancies | Kunstman et al., 2015 |
| EIF1AX | Xp22.12 | translation initiation factor, transfer of met-trnaf | Splice site 1 bp upstream of ex6 (C > G), G9R (C > G), P2R(G > C) | potential driver mutation | N/A | Kunstman et al., 2015, Landa et al., 2016 |
| ERBB2 | 17q12 | downstream enhancer of kinase-mediated signaling pathways | D387N | potential driver mutation | N/A | Kunstman et al., 2015 |
| D873N, A763T | N/A | Bonhomme et al., 2017 | ||||
| HECTD1 rs769574276 | 14q12 | ubiquitin protein ligase | L547 V | impairment of ubiquitynylated proteins degradation | N/A | Kunstman et al., 2015 |
| KMT2A, KMT2C, KMT2D (MLL2), SETD2 | 11q23.3, 7q36.1, 12q13.12, 3p21.31 | histone methyltransferases, epigenetic modifiers | N/A, KMT2D: Q1892Q (rs753626919), R5389W | impairment of epigenetic mechanisms, potential driver mutation | N/A, KMT2D: correlates with non-thyroidal malignancies | Landa et al., 2016, Kunstman et al., 2015 |
| MET | 7q31.2 | tyrosine-protein kinase met | I166T | proto-oncogene | N/A | Bonhomme et al., 2017 |
| mTOR | 1p36.22 | response element = to stress, possessing kinase activity | R164Q (rs573705289), M2327I | potential driver mutation | correlates with non-thyroidal malignancies | Kunstman et al., 2015 |
| NF1 | 17q11.2 | neurofibromatosis related gene | P2696L (rs778799019), R2496X (rs752162999) | potential driver mutation | correlates with non-thyroidal malignancies | Kunstman et al., 2015, Landa et al., 2016, Latteyer et al., 2016 |
| NOTCH1–4 (NOTCH2 in Kunstman) | 1p12 | transmembrane receptors | NOTCH2: S361F (rs587735797), R1393H | potential driver mutation | correlates with non-thyroidal malignancies | Kunstman et al., 2015, Landa et al., 2016 |
| PIK3CA | 3q26.32 | PI3K/AKT/mTOR pathway effector | E542K (rs121913273), E545K (rs104886003) | mutation of helical domain | N/A | Landa et al., 2016, Kunstman et al., 2015, Hou et al., 2007 |
| PTEN | 10q23.31 | PI3K/AKT/mTOR pathway effector | N/A | truncated protein | N/A | Landa et al., 2016, Hou et al., 2007 |
| RAS | 11p15.5, 1p13.2, 12p12.1 | signal transduction | N/A | preferential activation of PI3K-AKT pathway | N/A | Santarpia et al., 2008, Guerra et al., 2013, Landa et al., 2016, Latteyer et al., 2016, Hou et al., 2007 |
| TERT promoter | 5p15.33 | telomerase reverse transcriptase | C228T (rs35809415), C250T (rs1020948523) | gain of immortality | shorter survival | Bae et al., 2016, Landa et al., 2016 |
| TMPRSS4 | 11q23.3 | serine protease | N/A | promotes proliferation | positive correlation with tumor grade | Guan et al., 2015 |
| TP53 | 17p13.1 | tumor suppressor protein | Y163C (rs148924904) | gain of immortality | N/A | Kasaian et al., 2015, Landa et al., 2016, Bonhomme et al., 2017 |
| USH2A | 1q41 | uscherin, extracellular matrix binding protein interacting with collagen and fibronectin | I2189V (rs542406401), D798V (rs148431156), E571K(C > T), L1727F(G > A) | missense mutations | N/A | Kunstman et al., 2015 |
| CREBBP | 16p13.3 | histone acetyltransferase | N/A | epigenetic modifier | N/A | Landa et al., 2016 |
| EP300, BCOR, BCL6 | 22q13.2, Xp11.4, 3q27.3 | epigenetic modifiers | N/A | abnormal protein modifications | N/A | Landa et al., 2016 |
| CTNNB1 | 3p22.1 | cytoskeletal anchor, adhesive junctions | Q108H | unknown | N/A | Kunstman et al., 2015, Landa et al., 2016 |
| MSH2 | 2p21 | DNA mismatch repair | N/A | gain of mutation phenotype | N/A | Landa et al., 2016, Kunstman et al., 2015 |
| MSH5 | 6p21.33 | A199V (C > T) | N/A | |||
| MSH6 | 2p16.3 | D736H (G > C) | N/A | |||
| MLH1 | 3p22.2 | I19M (C > G), I68M (rs780141938), Q60X (C > T) | N/A | |||
| MLH3 | 14q24.3 | L264 V (G > C) | N/A | |||