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Table 1 Studies of thyroid cancer using next-generation sequencing platforms

From: Next-generation sequencing in thyroid cancer

Author (year) Diagnosis Patient number Sample type Platform Mutational panel Analytic process tool Important findings
Nikiforova et al. [10] Classic PTC 27 Fresh frozen tissue FFPE tissue Ion Torrent PGM ThyroSeq Torrent Suit version 3.4.2 1. 70% of classic PTCs harboring mutations: BRAF (59%) > PIK3A (11%) > TP53 (7%) > NRAS (4%)
FVPTC 30
2. 83% of FVPTC harboring mutations: RAS (73%) > BRAF (7%) > TSHR (3%)
Classic FC 18
3. Mutations of FC in order of frequency  Conventional type: NRAS > TSHR > KRAS  Oncocytic type: TP53 > HRAS > KRAS > PTEN
Oncocytic FC 18
4. 30% of PDCs harboring mutations of NRAS, PIK3CA, GNAS, BRAF and 74% of ACs harboring mutations of TP53, BRAF, RAS, PIK3CA, PTEN, CTNNB1
5. 11 MCs (73%) harboring mutations: 7 RET (47%), 3 HRAS (20%), 1 KRAS (7%)
PDC 10
AC 27
MC 15
Smallridge et al. [11] PTC, BRAF-mutant 12 Fresh frozen tissue Illumina HiSeq 2000 RNA-Seq (13085 genes) TopHat tool package 1. 51 genes related with immune function pathway are downregulated in BRAF V600E-mutant PTCs
2. HLAG, CXCL14, TIMP1, IL1RAP are overexpressed in BRAF V600E-mutant PTCs mutation
PTC, BRAF-wild type 8
Leeman-Neil et al. [12] PTC, radiation-associated 62 Fresh frozen tissue Illumina HiSeq 2000 RNA-Seq ChimeraScan and defuse program ETV6-NTRK3 rearrangement are present in 14.5% of radiation-associated PTCs and 2% of sporadic PTCs
PTC, sporadic 151
Simbolo et al. [32] MC 20 FFPE tissue Ion Torrent PGM Ion AmpliSeq Hot Spot Cancer Panel v2 (50 genes) Torrent Suit version 3.6 1. 85% of MCs have mutations: 13 RET (60%), 3 HRAS (15%), 1 KRAS (5%), 1 STK11 (5%), and 3 undetected (15%)
2. Three RET mutations are found by NGS test, which are negative by Sanger sequencing
Nikiforov et al. [34] FN/SFN 143 (retrospective group, N = 91; prospective group, N = = 52) FNA Ion Torrent PGM ThyroSeq v2 N/A Performance of NGS test in cancer detection among nodules with FN/SFN cytology: sensitivity 90%, specificity 93%, PPV 83%, NPV 96%, accuracy 92%
Cancer genome atlas research network [13] PTC 496 Fresh frozen tissue Illumina HiSeq 2000 Whole genome sequencing Picard pipeline 1. Identification of potential new tumor-initiating mutation in PTC lacking known driver mutation (EIF1AX, PPMID, CHEK2)
2. TERT promoter mutation (1%) associated with high risk of recurrence
3. Categorization of PTC into BRAF-like and RAS-like types based on the multi-level molecular data
Sykorova et al. [27] PDC 3 Fresh frozen tissue Illumina MiSeq The TruSight Cancer Panel (94 genes) MiSeq Reporter v.2.4 1. All PDC and AC harbor more than one genetic alteration, and TP53 mutation is commonly present except for 2 cases
2. Altered genes in PDCs: CDH1, FANCD2, CHECK2, ADH1B, GPC3, TP53, PTEN
3. Altered genes in ACs: ATM, HNF1A, MET, NF1, TP53, PTEN, MSH2, RB1, NBN, NF1, MUTYH, TSC2, HRAS, EGFR
AC 5
Le Mercier et al. [35] Indeterminate cytology 34 Cell blocks (FFPE) and smears Ion torrent PGM AmpliSeq Cancer hotspot panel version 2 Torrent Suit version 3.6.2 Performance of NGS test in cancer detection among nodules with indeterminate cytology: sensitivity 71%, specificity 89%, PPV 62%, NPV 92%, accuracy 85%
Ion AmpliSeq HiFi Master Mix Variant Caller plugin version 3.6
Nikiforov et al. [44] AUS/FLUS 465 FNA Ion torrent PGM Ion proton ThyroSeq v2.1 N/A Performance of NGS test in cancer detection among nodules with AUS/FLUS cytology: sensitivity 90.9%, specificity 92.1%, PPV 76.9%, NPV 97.2%, accuracy 91.8%
Picarsic et al. [14] PTC 17 (age <18 years) FNA Fresh frozen tissue FFPE tissue Ion Torrent PGM ThyroSeq v2 (14 gene and 42 types gene fusions) N/A 1. Mutation detection rate is increased from 60% with 7-gene mutation panel to 80% with NGS 2. Chromosomal rearrangement is more common than point mutation in pediatric PTC (53 vs. 33%) 3. ETV6-NTRK3 fusions are present in 18% and associated with unfavorable histology such as solid, insular, or trabecular patterns
Ballester et al. [15] PTC 25 (age range, 10–19 years) FNA FFPE tissue Ion torrent PGM AmpliSeq Cancer Hotspot Panel v2 (50 genes) Torrent Suit version 4.2 No additional mutation detected by NGS in cases lacking mutations in BRAF, RET/PTC, TERT promoter mutation at initial analysis
Landa et al. [28] PDC 34 Fresh frozen tissue (N = 37) FFPE tissue (N = 80) N/A MSK-IMPACT cancer exome panel (341 genes) MSK-IMPACT pipeline 1. Mutation number is greater in AC (6 ± 5) than PDC (2 ± 3), and predominantly affected genes are TP53, TERT promoter, PI3K/AKT/mTOR pathway effector, SWI/SNF subunit, and histone methyltransferase
2. 92% of RAS mutations are found in PDCs met Turin criteria; 81% BRAF mutations are present in PDCs met MSKCC criteria
3. BRAF-mutant PDCs are smaller and frequently metastasize to lymph nodes; RAS-mutant PDCs are larger and have higher frequency of distant metastasis
4. EIF1AX mutations are detected in 11% of PDCs and 9% of ACs, and 93% of which are associated with RAS mutations
5. Chromosomal rearrangement is detected in 14% of PDCs (RET/PTC, PAX8/PPARG, and ALK/EML4) and absent in AC
AC 33
Swierniak et al. [20] FA 26 Fresh frozen tissue Illumina HiSeq 1500 TruSeq panel (372 genes) Varscan2 CODEX package BreakDancer FACTERA 1. Common somatic alterations: oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK) 2. Single nucleotide variant is the most common and large structural variants are the least 3. Identification of novel translocation, DERL/COX6C
FC 20
PDC 2
Paired normal thyroid tissue 34
  1. AUS/FLUS atypia of undetermined significance/follicular lesion of undetermined significance, FNA fine needle aspiration, N/A not applicable, PPV positive predictive value, NPV negative predictive value, FN/SFN follicular or oncocytic (Hurthle cell) neoplasm/suspicious for a follicular or oncocytic (Hurthle cell) neoplasm, FFPE formalin-fixed, paraffin-embedded, PTC papillary thyroid carcinoma, FVPTC follicular variant papillary thyroid carcinoma, FC follicular carcinoma, PDC poorly differentiated carcinoma, AC anaplastic carcinoma, MSKCC Memorial Sloan-Kettering Cancer Center, MC medullary carcinoma