TP53 Expression and Mutational Analysis in Hematological Malignancy in Jeddah, Saudi Arabia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Cytogenetic and FISH Analysis
2.3. Next-Generation Sequencing Analysis
2.4. Data Analysis
2.5. Structural Analysis
3. Results
3.1. Clinical Characteristics of Patients
3.2. Cytogenetic and FISH Results
3.3. Next-Generation Sequencing Analysis
3.4. Correlation of TP53 Mutation with Cytogenetic & FISH Results
3.5. Correlation of TP53 Mutation with Other Genes Mutations
3.6. Structural and Functional Impact at the Protein Level
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene List (Targeted Exons) | |||||||
---|---|---|---|---|---|---|---|
GENE | EXON | GENE | EXON | GENE | EXON | GENE | EXON |
ASXL1 | 12 | EZH2 | 8, 17, 18 | MPL | 10 | SF3B1 | 13–15, 17 |
CSF3R | 14, 17 | FLT3 | 14, 20 | NPM1 | 11 | SRSF2 | 1 |
CBL | 8, 9 | IDH1 | 4 | NRAS | 2, 3 | TET2 | 3, 9, 10, 11 |
FFCEBPA | 1 | IDH2 | 4 | RUNX1 | 3, 4, 8 | TP53 | 5–8 |
DNMT3A | 4, 8, 13, 15, 16, 18–23 | JAK2 | 12, 14 | SETBP1 | 3 | U2AF1 | 2, 6 |
Case N.O. | Age | Sex | Diagnosis | Cytogenetic Result |
---|---|---|---|---|
1 | 2 | M | ALL | 46, XY |
2 | 2 | M | ALL | AL,57~43, XY, +X, dup (1) (q21q31), +4, +5, +6, +7, −8, +9, +10, +14, +17, +18, −19, −20, +21, +22 [cp50] |
3 | 5 | F | ALL | Leukemia,46, XX, der (19) t (1;19) (q25; p13.3) [17]/46, XX, idem, +der (21) t (1;21) (p13; p11.2) [14]/46, XX [19] |
4 | 5 | M | ALL | 46, XX [20] |
5 | 7 | F | ALL | 46, XX [20] |
6 | 9 | M | AML | 46, XY [20] |
7 | 12 | M | ALL | 46, XY, t (8; 21)(q22; q22) [29]/46, XY [21] |
8 | 31 | M | ALL | 46, XY [20] |
9 | 36 | F | AML | 46, XX [20] |
10 | 43 | M | AML | 46, XY [20] |
11 | 44 | F | ALL | ALL,45, XX, +X, −9, t (9;22) (q34; q11.2), −13[cp34]/45, XX, t (9;22) (q34; q11.2) [cp8]/46, XX[cp8] |
12 | 45 | F | ALL | 46, XX [20] |
13 | 59 | F | Lymphoma, NHL | 46, XX [20] |
14 | 63 | F | AML | 46, XX [20] |
15 | 65 | F | MDS | 65-58, XX, +1, +2, der(2) t(2;5) (q12; q37), +5, +6, +8, +9, +10, +11, der(17) t (12;17) (p10; p10), +13, del (13) (q21), +21, +21 [cp50] |
16 | 72 | M | AML | 45, XY,der (7;12), (q11.2; p12) [30] |
17 | 13 Y | F | AML | 46, XX [20] |
18 | 35 Y | F | AML | 46, XY [20] |
19 | 42 Y | M | AML | 46, XX [20] |
20 | 69 Y | M | AML | 46, XY [20] |
Diagnosis | Cytogenetic | FISH |
---|---|---|
NHL (1), ALL (5), AML (8) | Normal karyotype (14) | NHL TP53 deletion (1/1) (11%) |
ALL TP53 deletion (2/5) (20–22%) | ||
AML TP53 deletion (1/8) (11%) | ||
AML TP53 trisomy (1/8) (20%) | ||
ALL (1), AML (1) | Single abnormality (2) | ALL TP53 deletion (1/1) (22%) |
AML TP53 deletion (0/1) | ||
MDS (1), ALL (3) | Complex karyotype (4) | MDS (1/1) TP53 trisomy (30%) |
ALL (2/3) TP53 deletion (45%) |
Impacted Gene | TP53 |
---|---|
Type of Mutation | Missense mutation (Heterozygous) |
Chromosome | 17 |
Ref. Allele | T |
Alt. Allele | C |
Function Class | Missense |
AA | H175R |
Codon | cAt/cGt |
Quality | Pass |
Allele Frequency | 0.447 |
Number of Variant Alleles | 10,232 |
Filtered Read Depth (per sample) | 22,870 |
Effect | UNKNOWN |
Exon ID | NM_001126118.ex.5 |
Gene | Total No. of Mutation (n = 10) | TP53-Mutated (n = 1) | TP53-wt (n = 9) |
---|---|---|---|
ASXL1 | 10 | 1 | 9 |
CEBPA | 2 | 0 | 2 |
DNMT3A | 2 | 0 | 2 |
FLT3 | 2 | 0 | 2 |
IDH2 | 3 | 0 | 3 |
JAK2 | 1 | 0 | 1 |
NPM1 | 8 | 1 | 7 |
RUNX1 | 4 | 0 | 4 |
SETBP1 | 10 | 1 | 9 |
SRSF2 | 10 | 1 | 9 |
TET2 | 8 | 1 | 7 |
U2AF1 | 1 | 0 | 1 |
NRAS | 1 | 0 | 1 |
Sample No. | Age | Sex | Diagnosis | Gene | Type of Mutation |
---|---|---|---|---|---|
1 | 5 Y | F | ALL | ASXL1 | Missense (L815P) |
SETBP1 | Silent (S1275) | ||||
2 | 65 Y | F | MDS | ASXL1 | Missense (L815P) Missense (K1368T) |
SETBP1 | Missense (V231L) Silent (S1275) | ||||
3 | 59 Y | F | Lymphoma, NHL | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Missense (V1101I) Silent (S1275) | ||||
4 | 63 Y | F | AML | ASXL1 | Missense (L815P) |
SETBP1 | Silent (S1275) | ||||
5 | 36 Y | F | AML | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Silent (H1206) Silent (S1275) Silent (L1278) | ||||
6 | 43 Y | M | AML | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Silent (S1275) | ||||
7 | 13 Y | F | AML | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Silent (H1206) Silent (S1275) | ||||
8 | 35 Y | F | AML | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Missense (V1101I) Silent (S1275) | ||||
9 | 42 Y | M | AML | ASXL1 | Missense (L815P) Silent (S1253) |
SETBP1 | Silent (S1275) | ||||
10 | 69 Y | M | AML | ASXL1 | Missense (L815P) |
SETBP1 | Silent (S1275) |
Gene-Mutation | Polyphen-2 | I-Mutant 2.0 | ClinVar |
---|---|---|---|
TP53-R175H | POSSIBLY DAMAGING score: 0.881 (sensitivity: 0.82; specificity: 0.94) | Decrease in stability ΔΔG = −1.35 Kcal/mol | PATHOGENIC |
ASXL1-K1368T | BENIGN score: 0.091 (sensitivity: 0.93; specificity: 0.85) | Decrease in stability ΔΔG = −0.63 Kcal/mol | - |
SETBP1-V231L | BENIGN score: 0.006 (sensitivity: 0.97; specificity: 0.75) | Decrease in stability ΔΔG = −0.19 Kcal/mol | BENIGN |
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Alkhatabi, H.; Yasin, E.B.; Mirza, Z.; Alserihi, R.; Felimban, R.; Elaimi, A.; Shaabad, M.; Alharbi, L.; Ahmed, H.; Alameer, A.M.; et al. TP53 Expression and Mutational Analysis in Hematological Malignancy in Jeddah, Saudi Arabia. Diagnostics 2022, 12, 724. https://doi.org/10.3390/diagnostics12030724
Alkhatabi H, Yasin EB, Mirza Z, Alserihi R, Felimban R, Elaimi A, Shaabad M, Alharbi L, Ahmed H, Alameer AM, et al. TP53 Expression and Mutational Analysis in Hematological Malignancy in Jeddah, Saudi Arabia. Diagnostics. 2022; 12(3):724. https://doi.org/10.3390/diagnostics12030724
Chicago/Turabian StyleAlkhatabi, Heba, Elrashed B. Yasin, Zeenat Mirza, Raed Alserihi, Raed Felimban, Aisha Elaimi, Manal Shaabad, Lina Alharbi, Hameeda Ahmed, Abdulrahman M. Alameer, and et al. 2022. "TP53 Expression and Mutational Analysis in Hematological Malignancy in Jeddah, Saudi Arabia" Diagnostics 12, no. 3: 724. https://doi.org/10.3390/diagnostics12030724