Table 2 Somatic mutations characteristic of PTCs
Gene | Localization | Gene function | Mutation | Defect in cancer | Clinical correlation | Literature |
|---|---|---|---|---|---|---|
Gene | ||||||
BRAF | 7q34 | Serine/threonine kinase, response to cell growth factors | B-type Raf Kinase (chr 7) 2 Missense mutation V600E (T < A 1799), rs113488022 | Constitutive activation of MAPK pathway | Positive correlation with age, marker of TCV subtype | TCGA, Kimbrell et al., 2015, Lu et al., 2016, Gandolfi et al., 2013, Kim et al., 2006, Guerra et al., 2012, Sun et al., 2016, Gertz et al., 2016, Iyer et al., 2015, Lee et al., 2016 |
CHEK2 | 22q12.1 | Cell cycle checkpoint kinase | IVS2 + 1G > A, 1100delC or del5395, missense mutation I157T | DNA repair mechanism dysfunctions | Positive correlation with cancer aggressiveness | Siolek et al., 2015, Wójcicka et al., 2014, Kaczmarek-Ryś et al., 2015 |
DLL4 | 15q15.1 | Notch signaling mediator | Patient specific mutations | Promotes angiogenesis | Correlated with presence of lymph node metastases | Le Pennec et al., 2015 |
EIF1AX | Xp22.12 | Translation initiation factor, transfer of Met-tRNAf | Hotspot at A113_splice site intron 5/exon 6 | Potential driver mutation | N/A | TCGA, Forbes 2011, Martin 2013, Karanamurthy 2016 |
FOXE1 | 9q22.33 | Transcription factor | rs965513 AA, AG; rs944289; c.821C > A, p.P54Q; c.943A > C p.K95Q; c.994C > T, p.L112F | Deregulation of thyroid morphogenesis | Thyroid cancer susceptibility marker | Mond et al., 2015, Gudmundsson et al., 2009, Penna-Martinez et al., 2014 |
PIK3CA | 3q26.32 | PI3K/AKT/mTOR pathway effector | E545A | Mutation of helical domain | N/A | Lee et al., 2016 |
PTEN | 10q23.31 | PI3K/AKT/mTOR pathway effector | N/A | Produces a truncated protein | N/A | Xing et al., 2013 |
RAS | 11p15.5, 1p13.2, 12p12.1 | Signal transduction | H-Ras (chr11), N-Ras (chr1), K-Ras (chr12) | Preferential activation of PI3K-AKT pathway | Positive correlation with cancer aggressiveness | Rossi et al., 2015, Gertz et al., 2016, Abubaker et al., 2008, Zou et al., 2014 |
TERT promoter | 5p15.33 | Telomerase reverse transcriptase | C > T 1295228 and 1,295,250 C > A at 1295250 | Gain of immortality | Positive correlation with cancer aggressiveness | Bae et al., 2016, Liu et al., 2014, Liu et al., 2013, Sun et al., 2016 |
Chromosomal Abberations | ||||||
RET | 10q11.21 | Tyrosine kinase transmembrane receptor | Rearrangements: RET/PTC1, RET/PTC2, RET/PTC3, RET/PTC4. RET/PTC5, RET/PTC6, RET/PTC7, RET/PTC8, RET/PTC9, PCM1-RET, EKLS-RET, FKBP-RET, RET-ANK3, TBL1XR1-RET, AKAP13-RET, ERC1-RET, HOOK3-RET, SPECC1L-RET, ACBD5-RET, ΔRFP-RET | Downstream signaling of MAPK and PI3K pathways, evasion of apoptosis | Common in pediatric PTC, common co-occurrence with BRAF mutation | TCGA, Gertz et al., 2016, Rossi et al., 2015, Hamatani et al., 2014, Corvi et al., 2000, Ciampi et al., 2007, Klugbauer et al., 1998, Salassidis et al., 2000, Saenko et al., 2003, Nakata et al., 1999, Hamatani et al., 2014, Bongarzone et al., 1993, Grieco et al., 1990 |
Abnormal expression | ||||||
ATP5E | 20q13.32 | ATPase subunit 5E | Down-regulation | Disruption of ATP synthesis in mitochondria | Potential PTC biomarker | Hurtado-Lopez et al., 2015 |
MUC1 | 1q22 | Proliferation and signaling of epithelial cells | Overexpression | Leads to propagation of tumorigenesis and metastasis | Poor outcome marker | Renaud et al., 2014 |
TMPRSS4 | 11q23.3 | Serine protease | Overexpression | Migration and metastasis of cancer cells | Malignant tumors | Kebebew et al., 2005, Jarzab et al., 2005, Guan et al., 2015 |
YY1 | 14q32.2 | Transcription factor | Overexpression | Leads to increased cell proliferation | Positive correlation with age | Arribas et al., 2015 |
Regulation Of Expression | ||||||
micro RNA | Xp11.3 | Regulation of expression of affiliated genes | let-7 miRNA overexpression | Disruption of regulatory pathways (e.g. DNA damage response, stress response), propagation of cancer growth and expansion through down/up-regulation of target genes | N/A | Salajegheh et al., 2016, Yoruker et al., 2016, Lee et al., 2013, Zhang et al., 2010, Lei et al., 2016, Hong et al., 2016, Samsonov et al., 2016, Hu et al., 2017 |
9p21.3 | miR-31 overexpression | |||||
8q24.3 | miR-146b overexpression | |||||
19q13.41 | miR-151-5p overexpression | |||||
10q24.32 | miR-221 overexpression | |||||
Xp11.3 | miR-222 overexpression | |||||
17q23.1 | miR-21 down-regulation | |||||
9q34.3 | miR-126 down-regulation | |||||
19p13.12 | miR-20b | |||||
Xq26.2 | miR-639 | |||||