| Title |
Distinct Genomic Alterations in Prostate Tumors Derived from African American Men
|
|---|---|
| Published in |
Molecular Cancer Research, December 2020
|
| DOI | 10.1158/1541-7786.mcr-20-0648 |
| Pubmed ID | |
| Authors |
Wennuan Liu, S Lilly Zheng, Rong Na, Lin Wei, Jishan Sun, Johnie Gallagher, Jun Wei, W Kyle Resurreccion, Sarah Ernst, Karen S Sfanos, William B Isaacs, Jianfeng Xu |
| Abstract |
We aim to understand, from acquired genetic alterations in tumors, why African American (AA) men are more likely to develop aggressive prostate cancer. By analyzing somatic mutations in 39 genes using deeper next-generation sequencing with an average depth of 2,522 reads for tumor DNA and genome-wide DNA copy-number alterations (CNA) in prostate cancer in a total of 171 AA/black men and comparing with those in 860 European American (EA)/white men, we here present several novel findings. First, >35% of AA men harbor damaging mutations in APC, ATM, BRCA2, KDM6A, KMT2C, KMT2D, MED12, ZFHX3, and ZMYM3, each with >1% of mutated copies. Second, among genes with >10% of mutated copies in tumor cells, ZMYM3 is the most frequently mutated gene in AA prostate cancer. In a patient's tumor with >96% frameshift mutations of ZMYM3, we find allelic imbalances in 10 chromosomes, including losses of five and gains of another four chromosomes, suggesting its role in maintaining genomic integrity. Third, when compared to prostate cancer in EA/white men, a higher frequency of CNAs of MYC, THADA, NEIL3, LRP1B, BUB1B, MAP3K7, BNIP3L and RB1, and a lower frequency of deletions of RYBP, TP53, and TMPRSS2-ERG are observed in AA/black men. Finally, for the above genes with higher frequency of CNAs in AA than in EA, deletion of MAP3K7, BNIP3L, NEIL3 or RB1, or gain of MYC significantly associates with both higher Gleason grade and advanced pathologic stage in AA/black men. Deletion of THADA associates with advanced pathologic stage only. IMPLICATIONS: A higher frequency of damaging mutation in ZMYM3 causing genomic instability along with higher frequency of altered genomic regions including deletions of MAP3K7, BNIP3L, RB1, and NEIL3, and gain of MYC appear to be distinct somatically acquired genetic alterations that may contribute to more aggressive prostate cancer in AA/black men. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 20% |
| Student > Master | 4 | 16% |
| Student > Ph. D. Student | 3 | 12% |
| Unspecified | 2 | 8% |
| Other | 1 | 4% |
| Other | 3 | 12% |
| Unknown | 7 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 16% |
| Biochemistry, Genetics and Molecular Biology | 3 | 12% |
| Unspecified | 2 | 8% |
| Agricultural and Biological Sciences | 2 | 8% |
| Nursing and Health Professions | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 13 | 52% |
Attention Score in Context
This research output has an Altmetric Attention Score of 72. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2021.
All research outputs
#578,731
of 25,028,065 outputs
Outputs from Molecular Cancer Research
#24
of 2,011 outputs
Outputs of similar age
#16,086
of 522,377 outputs
Outputs of similar age from Molecular Cancer Research
#2
of 44 outputs
Altmetric has tracked 25,028,065 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,011 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 98% of its peers.
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