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A case report of multiple primary prostate tumors with differential drug sensitivity
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-8 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses of PTEN and TP53. The PTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies of PTEN and TP53, while the Gleason 7 PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.<br />Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.
- Subjects :
- Male
0301 basic medicine
Oncology
medicine.medical_treatment
General Physics and Astronomy
Drug resistance
Neoplasms, Multiple Primary
Androgen deprivation therapy
Prostate cancer
0302 clinical medicine
Prostate
Cancer genomics
Medicine
Neoplasm
lcsh:Science
Neoadjuvant therapy
Multidisciplinary
biology
Neoadjuvant Therapy
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
medicine.medical_specialty
Tumour heterogeneity
Science
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
Humans
PTEN
neoplasms
Aged
business.industry
PTEN Phosphohydrolase
Prostatic Neoplasms
Diagnostic markers
Androgen Antagonists
Sequence Analysis, DNA
General Chemistry
medicine.disease
030104 developmental biology
Drug Resistance, Neoplasm
Mutation
biology.protein
lcsh:Q
Cancer imaging
Neoplasm Grading
Tumor Suppressor Protein p53
business
Gene Deletion
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....aa3dee3836d30aaae03f289e7adf6b38