Table 1.
Studies evaluating somatic mutations in colorectal adenomas and cancers from patients with hereditary CRC syndromes.
| Syndrome | Study Population | Samples Analyzed | Study Methods | Frequent Mutated Genes and Candidate Driver Genes | Notes | References |
|---|---|---|---|---|---|---|
| FAP | 12 FAP patients | 25 adenomas, 10 adjacent NM |
WES | APC, KRAS, FBXW7, TCF7L2, BRCA2, ALK, CNOT3, ARID1A, CDC27, EWSR1, GNAQ, TTN, PCMTD1 | [32] | |
| FAP | 14 FAP patients | 37 adenomas and matched NM | Targeted Ampliseq sequencing | APC, KRAS | [33] | |
| FAP and MAP | 5 FAP patients 1 MAP patient |
20 LGD adenomas, 4 HGD adenomas, 7 carcinomas and 8 adjacent NM | WES, WGS |
APC (69%), TTN (37%), SMAD4 (35%), GNAS (33%), ASXL1 (33%), KRAS (23%), FAT4 (22%), ZFHX3 (22%), FBXW7 (22%), PTPRT (20%), SOX9 (16%) | Additional potential driver events with lower frequency: ERBB3 (8%), ARID1A (8%), TP53 (8%), ACVR2A (6%), EPHA5 (6%), TCF7L2 (6%), PIK3CA (6%), RBM10 (5%), CTNNB1 (5%), ATM (5%), AMER1 (5%). | [34] |
| FAP and MAP | 2 FAP patients and 2 MAP patients | 6 adenomas 8 adenomas |
WES | APC, KRAS, WTX/FAM123B, SCUBE2, RELN, FBXW7, MLL3, OTUD7B, KPRP, ATRNL1, MAP3K5, NRAS, PLCG2, PTEN, TP53 | Except for APC, WTX and KRAS, few adenomas shared the same set of mutated driver genes | [35] |
| 3 FAP patients and 4 MAP patients | 22 adenomas 33 adenomas |
Targeted exome sequencing | ||||
| 7 FAP patients and 3 MAP patients | 41 adenomas 22 adenomas |
WTX/KRAS capillary sequencing | ||||
| Lynch | 44 patients | 86 adenomas, 36 adenocarcinomas |
Target NGS | APC (40% of LS-associated adenomas, 28% of LS-adenocarcinomas and 60% sporadic adenomas); CTNNB1 (5% LS-adenomas and 10% sporadic adenomas); RNF43 (52% LS-associated adenomas; 56% LS-adenocarcinomas). |
KRAS, BRAF and NRAS mutations uncommon in both LS- and sporadic adenomas |
[36] |
| 84 sporadic adenomas | ||||||
| Lynch | 57 patients | 59 adenomas: 16 MMR-P; 43 MMR-D (41 LGD and 18 HGD) | Amplicon-based NGS | TP53 (24%), KRAS (22%), SMAD4 (19%), CTNNB1 (15%) | Additional potential driver events with lower frequency: ALK (2%), BRAF (9%), DDR2 (2%), EGFR (10%), ERBB2 (3%), ERBB4 (5%), FBXW7 (9%), FGFR1 (2%), FGFR2 (3%), MET (2%), NOTCH1 (5%), PTEN (10%), PIK3CA (5%), STKI1 (3%) | |
| [37] | ||||||
| Lynch | 11 patients | Paired tumor (adenoma and cancer) and tumor-distant NM | Whole- genome DNA- sequencing | ACVR2A, TGFBR2, CDC27, AIM2, PDS5B, TP53, KRAS (Frequent in the G1 LS-CRC subgroup) | Paired patient-matched specimens of tumors were stratified into two subgroups based on their genomic characteristics (G1 with higher amount of mutation and MS slippage than G2) | [38] |
FAP (Familial Adenomatous Polyposis); MAP (MUTYH-associated Polyposis); NM (Normal Mucosa); LGD (Low-Grade Dysplasia); HGD (High-Grade Dysplasia); WES (Whole-Exome Sequencing); WGS (Whole-Genome Sequencing); NGS (Next-Generation Sequencing); MMR-P (MMR-proficient); MMR-D (MMR-deficient); MS (microsatellite). The frequency of mutations (%) is shown for those studies that have reported them.