Table 1.
Summary of observed CNAs. Gene functions, alteration types, and implications are displayed with the frequencies of occurrence in MTCs, BMTP, and PTTP
| Gene | Function | Type of alteration | MTCs | BMTP | PTTP | Implications |
|---|---|---|---|---|---|---|
| PTEN | Tumor suppressor | Deletion | 77% (17/22) | 0% (0/17) | 34% (11/32) | Increased cell proliferation and reduced cell death due to dysfunction in cell cycle regulation |
| RB1 | Tumor suppressor | Hemizygous Deletion | 0% (0/22) | 23% (4/17) | 0% (0/32) | Excessive cell growth due to dysregulation of cell cycle inhibition |
| TP53 | Tumor suppressor | Deletion | 68% (15/22) | 82% (14/17) | 0% (0/32) | Dysfunction in DNA repair activation, cell cycle inhibition, activation of apoptosis and senescence response to short telomeres |
| ATM | Coordinates DNA repair | Deletion | 77% (17/22) | 94% (16/17) | 47% (15/32) | Dysfunction in recognition of DNA damage and activation of DNA repair pathways |
| BRCA1 | Tumor suppressor DNA repair | Deletion | 9% (2/22) | 29% (5/17) | 9% (3/32) | Dysfunction in repairing damaged DNA properly. Cell can no longer sense DNA damage and sent appropriate signals |
| BRCA2 | Tumor suppressor DNA repair | Hemizygous deletion | 0% (0/22) | 23% (4/17) | 0% (0/32) | Dysfunction in repairing damaged DNA properly. BRCA2 directly binds DNA and interact with other protein to initiation strand invasion during repair |
| CDK2 | Cell cycle regulator | Deletion | 36% (8/22) | 23% (4/17) | 9% (3/32) | Dysfunction in cell cycle regulation specifically G1-S transition |
| MLH1 | DNA mismatch repair | Deletion | 0% (0/22) | 2% (3/17) | 19% (6/32) | Dysfunction in DNA specifically in recognition and initiation of mismatch repair, therefore, elevating spontaneous mutation rate |
| NCOA2 | Transcription co-regulator | Amplification | 68% (15/22) | 100% (17/17) | 28% (9/32) | Upregulation of DNA expression for nuclear hormone receptors such as AR and ESR1 |
| MYC | Transcription factor | Amplification | 0% (0/22) | 12% (2/17) | 3% (1/32) | Upregulation of many genes involved in cell proliferation and cellular transformation via DNA over-replication |
| NKX3.1 | Tumor suppressor | Deletion | 73% (16/22) | 94% (16/17) | 50% (16/32) | As a transcription factor with critical function in prostate development NKX3.1 deletion results in increase prostate epithelial cell growth |
| AR | Transcription factor | Amplification | 0% (0/22) | 0% (0/17) | 0% (0/32) | As a transcription factor, AR amplification results in DNA over expression of genes such as IGFR and PSA that promote cell proliferation |
| ETV6 | Transcription factor | Deletion | 45% (10/22) | 41% (7/17) | 6% (2/32) | As a transcription factor it interacts with DNA to mostly inhibit transcription of its target genes that regulate both differentiation and cell growth |
| polyploidy | — | Numerical change in a whole set of chromosomes | 64% (14/22) | 0% (0/17) | 0% (0/32) | Polyploidy occurs due to abnormal cell division and have associated with TP53 deletion |