NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas
Abstract
:1. Introduction
2. Results
2.1. Clinicopathologic Characteristics
2.2. Mutations in Sebaceous Carcinoma
2.3. Copy Number Variations in Sebaceous Carcinoma
2.4. MYC Fluorescence In Situ Hybridization (FISH)
2.5. MYC Immunohistochemistry
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. DNA Extraction and Next-Generation Sequencing
4.3. MYC Fluorescence In Situ Hybridization
4.4. MYC Immunohistochemistry
4.5. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Case Number | Sex | Age (years) | Tumor Type | Tumor Location | Tumor Laterality | Epithelial Involvement | T Stage | History of Malignancy |
---|---|---|---|---|---|---|---|---|
1 | F | 54 | OA | Upper lid | Left | None | T1 | None |
2 | M | 77 | OA | Upper lid | Right | Intraepithelial | T1 | None |
3 | M | 83 | OA | Upper lid | Left | Combined | T1 | Non-cutaneous |
4 | F | 80 | OA | Upper lid | Right | Combined | T1 | None |
5 | M | 87 | OA | Upper lid | Left | Combined | T1 | None |
6 | F | 60 | OA | Upper lid | Right | Combined | T1 | None |
7 | F | 82 | OA | Upper lid | Left | Combined | T2 | Cutaneous |
8 | M | 83 | OA | Upper lid | Right | Subepithelial | T1 | Non-cutaneous |
9 | F | 90 | OA | Upper lid | Right | Subepithelial | T2 | None |
10 | F | 55 | OA | Lower lid | Right | Combined | T1 | Cutaneous |
11 | M | 43 | OA | Upper lid | Right | None | T1 | Non-cutaneous |
12 | F | 58 | EO | Lateral breast | Left | None | T1 | Multiple 1 |
13 | M | 87 | EO | Post-auricular neck | Left | None | T1 | Cutaneous |
Case Number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mutations in Clinically Actionable Genes | |||||||||||||
ABL1 | p.E197K | ||||||||||||
ATM | p.Q2433Pfs*11 | p.I2669Yfs*6 | |||||||||||
BRCA1 | p.K1487I | p.R1726G | NE | ||||||||||
BRCA2 | p.L2510_Y2511insKTCN | NE | |||||||||||
EGFR | p.P772S | p.Q976Pfs*9 | |||||||||||
FGFR2 | p.S702L | ||||||||||||
FGFR3 | p.F384L | p.R728W | |||||||||||
HRAS | p.P167Rfs*50, p.P167R | p.P167Rfs*50 | |||||||||||
IDH2 | p.V335I | ||||||||||||
MLH1 | p.E694X | ||||||||||||
MSH2 | NE | p.Q409Rfs*4, p.Q409R, p.Q409H, p.I679T | |||||||||||
MSH6 | p.V526L | NE | |||||||||||
MTOR | p.L93Qfs*28 | p.P677S | NE | ||||||||||
NF1 | p.K1915T | NE | p.I679Dfs*20, p.C1924Wfs*3 | ||||||||||
NTRK1 | p.H467Q | NE | |||||||||||
NTRK3 | p.R169C | p.Y604H | NE | ||||||||||
PALB2 | p.S417Y | p.R1117Sfs*8 | NE | ||||||||||
PDGFRA | p.E241X | ||||||||||||
PIK3CA | p.V101fs*0 | ||||||||||||
PMS2 | p.V397I | p.S418F | p.L236Sfs*3 | p.L236delinsYLLKKIM | NE | ||||||||
POLD1 | NE | p.A242T | |||||||||||
PTCH2 | NE | p.G1023S, p.E48del | |||||||||||
PTEN | p.P281A | ||||||||||||
RB1 | p.? (Unknown) | p.? (Unknown) | p.Q354Efs*5 | p.W75X, p.R358X | p.? (Unknown) | p.E30X | p.R500I | ||||||
RET | p.A349V | ||||||||||||
ROS1 | p.F1300L | p.D2344N | p.L2337F | NE | |||||||||
SMO | p.L23_G24insL | ||||||||||||
TERT | p.A279T | NE | |||||||||||
TP53 | p.R273C | p.G266R | p.? (Unknown) | p.C277F | p.R273C | p.G245S | p.L257P | p.? (Unknown) | p.E339X | p.R196* | |||
TSC1 | p.G274S | NE | |||||||||||
TSC2 | p.G440S | NE | |||||||||||
Genes with Frequent Mutations (≥ 25%) | |||||||||||||
KMT2C | p.A1685S | p.S888T | NE | p.K2797Rfs*25 | p.K2797Rfs*25 | ||||||||
MNX1 | p.A134_G135insAA | p.A174del | p.A134_G135insAA | p.A134_G135insAA | p.A134_G135insAA | p.A134_G135insAA | NE | ||||||
NOTCH1 | p.G1320Afs*124 | p.Y550fs*0 | NE | p.R203C | p.L1531Cfs*48, p.P1443Afs*35 | ||||||||
PCLO | p.G1750E | p.P2128Q | NE | p.E2925D | |||||||||
PTPRT | p.R1209Q | p.R260W | NE | p.P1094Rfs*5 | |||||||||
MYC Gain of Copy | |||||||||||||
Mean log2 Ratio | <0.5 | NE | <0.5 | 0.833 | 0.8959 | 0.5483 | 0.8178 | 1.3315 | 1.4416 | <0.5 | NE | 0.7733 | 0.6051 |
Variable | All Cases (n = 11) n (%) | No MYC Copy Gain (n = 3) n (%) | MYC Copy Gain (n = 8) n (%) | p Value |
---|---|---|---|---|
Sex | ||||
Male Female | 4 (36) 7 (64) | 1 (33) 2 (67) | 3 (37) 5 (63) | 1.00 |
Age (years), mean ± SD | 73 ± 13.8 | 64 ± 16.4 | 76 ± 12.3 | 0.53 |
Tumor site Ocular adnexal Extraocular | 9 (82) 2 (18) | 3 (100) 0 (0) | 6 (75) 2 (25) | 1.00 |
Tumor location (OA: n = 9) Upper lid Lower lid | 7 (78) 2 (22) | 2 (67) 1 (33) | 5 (83) 1 (17) | 1.00 |
Tumor laterality (OA: n = 9) Right Left | 5 (56) 4 (44) | 1 (33) 2 (67) | 4 (67) 2 (33) | 0.52 |
Variable | All Cases (n = 11) n (%) | No MYC Copy Gain (n = 3) n (%) | MYC Copy Gain (n = 8) n (%) | p Value |
---|---|---|---|---|
MYC expression (IHC) | ||||
Low High | 5 (45) 6 (55) | 1 (33) 2 (67) | 4 (50) 4 (50) | 1.00 |
Tumor size (mm), mean ± SD | 7.7 ± 2.6 | 6.5 ± 0.7 | 8.0 ± 2.9 | 0.50 |
TP53 Mutation WT | 8 (73) 3 (27) | 2 (67) 1 (33) | 6 (75) 2 (25) | 1.00 |
RB1 Mutation WT | 6 (55) 5 (45) | 2 (67) 1 (33) | 4 (50) 4 (50) | 1.00 |
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Peterson, C.; Moore, R.; Hicks, J.L.; Morsberger, L.A.; De Marzo, A.M.; Zou, Y.; Eberhart, C.G.; Campbell, A.A. NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas. Int. J. Mol. Sci. 2021, 22, 8454. https://doi.org/10.3390/ijms22168454
Peterson C, Moore R, Hicks JL, Morsberger LA, De Marzo AM, Zou Y, Eberhart CG, Campbell AA. NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas. International Journal of Molecular Sciences. 2021; 22(16):8454. https://doi.org/10.3390/ijms22168454
Chicago/Turabian StylePeterson, Cornelia, Robert Moore, Jessica L. Hicks, Laura A. Morsberger, Angelo M. De Marzo, Ying Zou, Charles G. Eberhart, and Ashley A. Campbell. 2021. "NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas" International Journal of Molecular Sciences 22, no. 16: 8454. https://doi.org/10.3390/ijms22168454