APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
3. Distribution of APC Mutations
4. Microsatellite Instability
5. Loss of Heterozygosity is Associated with APC Mutation Near Codon 1300
6. Methylation of the APC Promoter
7. Discussion
8. Methods
8.1. Cohort
8.2. DNA Extraction
8.3. Sequencing Library Preparation
8.4. Sequence Analysis and Annotation
8.5. LOH at APC Locus
Sanger Sequencing
8.6. Microsatellite Instability
8.7. Bisulphite Treatment and Methylation Analysis
9. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Number | % | |
---|---|---|
Total | 25 | |
Gender | ||
Male | 11 | 44 |
Female | 14 | 56 |
Age at diagnosis (years) | ||
<30 | 1 | 4 |
31–40 | 6 | 24 |
41–50 | 18 | 72 |
Tumour site | ||
Caecum | 1 | 4 |
Ascending colon | 6 | 24 |
Hepatic flexure | 1 | 4 |
Splenic flexure | 1 | 4 |
Descending colon | 3 | 12 |
Sigmoid colon | 12 | 48 |
Rectosigmoid | 1 | 4 |
Pathology | ||
Adenocarcinoma | 23 | 92 |
Adenosquamous carcinoma | 1 | 4 |
Signet-ring cell carcinoma | 1 | 4 |
Patient Number | Microsatellite Instability | Mutation | Mutational Outcome | Mutational Assessment 1 | APC Methylation | LOH | Reference | ||
---|---|---|---|---|---|---|---|---|---|
DNA | rsID | Protein | |||||||
10006 | MSI | c.2626C>T | rs121913333 | p.R876X | Nonsense | Damaging | U | - | [32] |
10765 | MSS | c.835-8A>G | rs1064793022 | Splice variant | Truncation 2 | Damaging | U | - | [33] |
12294 | MSS | c.1660C>T | rs137854573 | p.R554X | Nonsense | Damaging | M | - | [34] |
12961 | MSS | c.2853T>G | rs575406600 | p.Y951X | Nonsense | Damaging | M | - | [34] |
13046 | MSS | c.4488delT | n/a | p.P1497fsX | Frameshift | Damaging | U | - | This Study |
c.2805C>A | rs137854575 | p.Y935X | Nonsense | Damaging | [35] | ||||
13501 | MSS | c.2636delA | n/a | p.Q879fsX | Frameshift | Damaging | U | - | This Study |
13564 | MSS | c.4033G>T | rs1211642532 | P.E1345X | Nonsense | Damaging | U | LOH | [36] |
14459 | MSS | c.4463delT | rs1114167577 | p.L1488fsX | Frameshift | Damaging | M | - | [37] |
c.3826delT | n/a | p.S1276fsX | Frameshift | Damaging | This Study | ||||
15052 | MSS | - | - | - | - | - | M | - | - |
15296 | MSS | - | - | - | - | - | U | - | - |
15310 | MSS | c.4216C>T | rs587782518 | p.Q1406X | Nonsense | Damaging | U | LOH | [38] |
c.3949G>C | rs1801166 | p.E1317Q | Missense | Benign | [39] | ||||
15471 | MSS | - | - | - | - | - | M | - | - |
16872 | MSS | - | - | - | - | - | U | - | - |
16993 | MSS | c.4717G>T | rs878853217 | p.E1573X | Nonsense | Damaging | U | - | [40] |
c.2821G>T | n/a | p.E941X | Nonsense | Damaging | [37] | ||||
17068 | MSS | - | - | - | - | - | M | - | - |
17871 | MSS | c.4485delT | n/a | p.S1459fsX | Frameshift | Damaging | U | - | This Study |
c.2626C>T | rs121913333 | p.R876X | Nonsense | Damaging | [32] | ||||
18090 | MSS | c.3925G>T | n/a | p.E1309X | Nonsense | Damaging | M | LOH | [27] |
19199 | MSS | c.646C>T | rs62619935 | p.R216X | Nonsense | Damaging | U | - | [36] |
19513 | MSS | c.3740C>T | n/a | p.A1247V | Missense | Benign | M | - | This Study |
c.3340C>T | rs121913331 | p.R1114X | Nonsense | Damaging | [40] | ||||
19906 | MSS | - | - | - | - | - | U | - | - |
20039 | MSS | c.4230C>A | n/a | p.C1410X | Nonsense | Damaging | U | - | This Study |
20085 | MSI | c.694C>T | rs397515734 | p.R232X | Nonsense | Damaging | M | - | [35] |
20187 | MSS | c.3374T>C | rs377278397 | p.V1125A | Missense | Benign | U | - | [41] |
21025 | MSI | c.2563_2564dupGA | n/a | p.R856fsX | Frameshift | Damaging | M | - | This Study |
21082 | MSS | - | - | - | - | - | U | - | - |
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Aitchison, A.; Hakkaart, C.; Day, R.C.; Morrin, H.R.; Frizelle, F.A.; Keenan, J.I. APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer. Cancers 2020, 12, 3829. https://doi.org/10.3390/cancers12123829
Aitchison A, Hakkaart C, Day RC, Morrin HR, Frizelle FA, Keenan JI. APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer. Cancers. 2020; 12(12):3829. https://doi.org/10.3390/cancers12123829
Chicago/Turabian StyleAitchison, Alan, Christopher Hakkaart, Robert C. Day, Helen R. Morrin, Frank A. Frizelle, and Jacqueline I. Keenan. 2020. "APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer" Cancers 12, no. 12: 3829. https://doi.org/10.3390/cancers12123829