Journal article
A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men
Uniformed Services University of the Health Sciences1
National Cancer Institute United States2
Massachusetts General Hospital/Harvard Medical School3
Heidelberg University 4
Genomatix AG5
Xiamen University6
Technical University of Denmark7
CytoTest Inc.8
The Joint Pathology Center9
Department of Systems Biology, Technical University of Denmark10
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark11
Cancer Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark12
...and 2 moreEvaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes.
We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression.
In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.
| Language: | English |
|---|---|
| Publisher: | Elsevier |
| Year: | 2015 |
| Pages: | 1957-1964 |
| ISSN: | 23523964 |
| Types: | Journal article |
| DOI: | 10.1016/j.ebiom.2015.10.028 |
Aged Biomarkers, Tumor Black or African American Cell Adhesion Molecules, Neuronal Cluster Analysis Disease Progression GPI-Linked Proteins Gene Deletion Gene Rearrangement Genetic Association Studies Genetic Loci Genetic Variation Genomics High-Throughput Nucleotide Sequencing Humans Male Medicine Medicine (General) Middle Aged Mutation Neoplasm Grading Neoplasm Staging Oncogene Proteins, Fusion PTEN Phosphohydrolase PTEN protein, human Polymorphism, Single Nucleotide Prostatic Neoplasms R R5-920 Reproducibility of Results TMPRSS2-ERG fusion protein, human limbic system-associated membrane protein
