Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer.
diagnostic biopsy
genomic heterogeneity
multifocal tumors
pathology
prostate cancer
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
25
01
2019
revised:
28
02
2019
accepted:
04
03
2019
pubmed:
26
3
2019
medline:
15
1
2020
entrez:
26
3
2019
Statut:
ppublish
Résumé
The majority of clinical prostate cancers are multifocal with morphological and molecular heterogeneity. Adequate tissue representation is crucial for the clinical utility of multigene panel sequencing of core needle biopsies. The aim of this study was to evaluate the genomic heterogeneity in multifocal prostate cancer and to analyze how representative preoperative biopsies are of spatially separated tumor foci. We analyzed at least 2 tumor foci and 1 to 3 preoperative biopsy cores from 11 patients. Diagnostic biopsies, as well as fresh frozen and formalin-fixed paraffin-embedded samples, from major tumor foci of radical prostatectomy specimens were macrodissected for the enrichment of tumor tissue. DNA was extracted and sequenced. We analyzed structural alterations, mutations, and copy number variations and compared the genomic profiles of tumor foci with those of preoperative biopsies. Alterations were rarely shared between foci, indicating a high degree of genomic heterogeneity. In 8 of 11 men at least 1 tumor focus was represented by the biopsies defined as harboring at least 1 common clonal somatic event. In only one case, somatic alterations from two spatially separate tumors were identified in the biopsies. Of the mutations and structural variants detected in fresh frozen or formalin-fixed paraffin-embedded prostatectomy material, only an average of 19% (range 0-44) and 55% (range 0-100), respectively, were found in preoperative biopsies where a common somatic origin was established. Multifocal prostate cancer is a somatically heterogeneous disease in which systematic needle biopsies do not provide sufficient molecular representation of the somatic alterations detected in spatially distinct tumor areas. Targeted biopsies, directed at separate tumor foci, could potentially improve tissue representation of these heterogeneous foci in preoperative biopsies.
Sections du résumé
BACKGROUND
The majority of clinical prostate cancers are multifocal with morphological and molecular heterogeneity. Adequate tissue representation is crucial for the clinical utility of multigene panel sequencing of core needle biopsies. The aim of this study was to evaluate the genomic heterogeneity in multifocal prostate cancer and to analyze how representative preoperative biopsies are of spatially separated tumor foci.
METHODS
We analyzed at least 2 tumor foci and 1 to 3 preoperative biopsy cores from 11 patients. Diagnostic biopsies, as well as fresh frozen and formalin-fixed paraffin-embedded samples, from major tumor foci of radical prostatectomy specimens were macrodissected for the enrichment of tumor tissue. DNA was extracted and sequenced. We analyzed structural alterations, mutations, and copy number variations and compared the genomic profiles of tumor foci with those of preoperative biopsies.
RESULTS
Alterations were rarely shared between foci, indicating a high degree of genomic heterogeneity. In 8 of 11 men at least 1 tumor focus was represented by the biopsies defined as harboring at least 1 common clonal somatic event. In only one case, somatic alterations from two spatially separate tumors were identified in the biopsies. Of the mutations and structural variants detected in fresh frozen or formalin-fixed paraffin-embedded prostatectomy material, only an average of 19% (range 0-44) and 55% (range 0-100), respectively, were found in preoperative biopsies where a common somatic origin was established.
CONCLUSIONS
Multifocal prostate cancer is a somatically heterogeneous disease in which systematic needle biopsies do not provide sufficient molecular representation of the somatic alterations detected in spatially distinct tumor areas. Targeted biopsies, directed at separate tumor foci, could potentially improve tissue representation of these heterogeneous foci in preoperative biopsies.
Substances chimiques
DNA, Neoplasm
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
920-928Informations de copyright
© 2019 Wiley Periodicals, Inc.