Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer
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 heterogeneit...
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| Veröffentlicht in: | The Prostate 2019-06, Vol.79 (8), p.920-928 |
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| creator | Kristiansen, Anna Bergström, Rebecka Delahunt, Brett Samaratunga, Hemamali Guðjónsdóttir, Jóna Grönberg, Henrik Egevad, Lars Lindberg, Johan |
| description | 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. |
| doi_str_mv | 10.1002/pros.23797 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_481038</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2220300477</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4457-4043be82472a0df46ea78afda0f7df39ee54830efa47d71c055251832d852b083</originalsourceid><addsrcrecordid>eNp9kk9rFjEQxoMo9rV68QPIghcRtk7-bJM9SrEqFCpWzyGbTCR1d7NNdi09-dWbdd-2IOgpw-T3PJnMDCEvKRxRAPZuSjEfMS5b-YjsKLSyBhDNY7IDJqEWlMsD8iznS4CCA3tKDji0oI4l7MjviziYOdjK9DOmEsUxVw5ntDO6KoyVC-bHGPOKrO_MZsaqC3HKAfOa-RUcVmYsqHF4tazXCaeEGcf5j10VfTUs_Rx8tKZ_MLFmtJiekyfe9Blf7M9D8v30w7eTT_XZ-cfPJ-_PaitEI2sBgneomJDMgPPiGI1UxjsDXjrPW8RGKA7ojZBOUgtNwxqqOHOqYR0ofkjqzTdf47R0ekphMOlGRxP0PvWzRKiFosBXvv0nX77gHkR3QipASdoCFO2bTVvAqwXzrIeQLfa9GTEuWTPaSqUawWlBX_-FXsYljaUTmjEGvAxSykK93ShbmpcT-vtyKOh1BdaSimJdgQK_2lsu3YDuHr2beQHoBlyHHm_-Y6W_fD2_2ExvAfCkv-Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2220300477</pqid></control><display><type>article</type><title>Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Kristiansen, Anna ; Bergström, Rebecka ; Delahunt, Brett ; Samaratunga, Hemamali ; Guðjónsdóttir, Jóna ; Grönberg, Henrik ; Egevad, Lars ; Lindberg, Johan</creator><creatorcontrib>Kristiansen, Anna ; Bergström, Rebecka ; Delahunt, Brett ; Samaratunga, Hemamali ; Guðjónsdóttir, Jóna ; Grönberg, Henrik ; Egevad, Lars ; Lindberg, Johan</creatorcontrib><description>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.</description><identifier>ISSN: 0270-4137</identifier><identifier>ISSN: 1097-0045</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.23797</identifier><identifier>PMID: 30908670</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Biopsy ; Biopsy, Large-Core Needle - methods ; Cancer surgery ; Copy number ; diagnostic biopsy ; DNA, Neoplasm - genetics ; Formaldehyde ; Genetic Heterogeneity ; genomic heterogeneity ; Humans ; Male ; Medicin och hälsovetenskap ; multifocal tumors ; Mutation ; Nucleotide sequence ; Paraffin ; pathology ; Prostate cancer ; Prostatectomy ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Tumors ; Urological surgery</subject><ispartof>The Prostate, 2019-06, Vol.79 (8), p.920-928</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4457-4043be82472a0df46ea78afda0f7df39ee54830efa47d71c055251832d852b083</citedby><cites>FETCH-LOGICAL-c4457-4043be82472a0df46ea78afda0f7df39ee54830efa47d71c055251832d852b083</cites><orcidid>0000-0002-1916-7738</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.23797$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.23797$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30908670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:140871900$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Kristiansen, Anna</creatorcontrib><creatorcontrib>Bergström, Rebecka</creatorcontrib><creatorcontrib>Delahunt, Brett</creatorcontrib><creatorcontrib>Samaratunga, Hemamali</creatorcontrib><creatorcontrib>Guðjónsdóttir, Jóna</creatorcontrib><creatorcontrib>Grönberg, Henrik</creatorcontrib><creatorcontrib>Egevad, Lars</creatorcontrib><creatorcontrib>Lindberg, Johan</creatorcontrib><title>Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>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.</description><subject>Biopsy</subject><subject>Biopsy, Large-Core Needle - methods</subject><subject>Cancer surgery</subject><subject>Copy number</subject><subject>diagnostic biopsy</subject><subject>DNA, Neoplasm - genetics</subject><subject>Formaldehyde</subject><subject>Genetic Heterogeneity</subject><subject>genomic heterogeneity</subject><subject>Humans</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>multifocal tumors</subject><subject>Mutation</subject><subject>Nucleotide sequence</subject><subject>Paraffin</subject><subject>pathology</subject><subject>Prostate cancer</subject><subject>Prostatectomy</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Tumors</subject><subject>Urological surgery</subject><issn>0270-4137</issn><issn>1097-0045</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk9rFjEQxoMo9rV68QPIghcRtk7-bJM9SrEqFCpWzyGbTCR1d7NNdi09-dWbdd-2IOgpw-T3PJnMDCEvKRxRAPZuSjEfMS5b-YjsKLSyBhDNY7IDJqEWlMsD8iznS4CCA3tKDji0oI4l7MjviziYOdjK9DOmEsUxVw5ntDO6KoyVC-bHGPOKrO_MZsaqC3HKAfOa-RUcVmYsqHF4tazXCaeEGcf5j10VfTUs_Rx8tKZ_MLFmtJiekyfe9Blf7M9D8v30w7eTT_XZ-cfPJ-_PaitEI2sBgneomJDMgPPiGI1UxjsDXjrPW8RGKA7ojZBOUgtNwxqqOHOqYR0ofkjqzTdf47R0ekphMOlGRxP0PvWzRKiFosBXvv0nX77gHkR3QipASdoCFO2bTVvAqwXzrIeQLfa9GTEuWTPaSqUawWlBX_-FXsYljaUTmjEGvAxSykK93ShbmpcT-vtyKOh1BdaSimJdgQK_2lsu3YDuHr2beQHoBlyHHm_-Y6W_fD2_2ExvAfCkv-Y</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Kristiansen, Anna</creator><creator>Bergström, Rebecka</creator><creator>Delahunt, Brett</creator><creator>Samaratunga, Hemamali</creator><creator>Guðjónsdóttir, Jóna</creator><creator>Grönberg, Henrik</creator><creator>Egevad, Lars</creator><creator>Lindberg, Johan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-1916-7738</orcidid></search><sort><creationdate>20190601</creationdate><title>Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer</title><author>Kristiansen, Anna ; Bergström, Rebecka ; Delahunt, Brett ; Samaratunga, Hemamali ; Guðjónsdóttir, Jóna ; Grönberg, Henrik ; Egevad, Lars ; Lindberg, Johan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4457-4043be82472a0df46ea78afda0f7df39ee54830efa47d71c055251832d852b083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biopsy</topic><topic>Biopsy, Large-Core Needle - methods</topic><topic>Cancer surgery</topic><topic>Copy number</topic><topic>diagnostic biopsy</topic><topic>DNA, Neoplasm - genetics</topic><topic>Formaldehyde</topic><topic>Genetic Heterogeneity</topic><topic>genomic heterogeneity</topic><topic>Humans</topic><topic>Male</topic><topic>Medicin och hälsovetenskap</topic><topic>multifocal tumors</topic><topic>Mutation</topic><topic>Nucleotide sequence</topic><topic>Paraffin</topic><topic>pathology</topic><topic>Prostate cancer</topic><topic>Prostatectomy</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Tumors</topic><topic>Urological surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kristiansen, Anna</creatorcontrib><creatorcontrib>Bergström, Rebecka</creatorcontrib><creatorcontrib>Delahunt, Brett</creatorcontrib><creatorcontrib>Samaratunga, Hemamali</creatorcontrib><creatorcontrib>Guðjónsdóttir, Jóna</creatorcontrib><creatorcontrib>Grönberg, Henrik</creatorcontrib><creatorcontrib>Egevad, Lars</creatorcontrib><creatorcontrib>Lindberg, Johan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kristiansen, Anna</au><au>Bergström, Rebecka</au><au>Delahunt, Brett</au><au>Samaratunga, Hemamali</au><au>Guðjónsdóttir, Jóna</au><au>Grönberg, Henrik</au><au>Egevad, Lars</au><au>Lindberg, Johan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>79</volume><issue>8</issue><spage>920</spage><epage>928</epage><pages>920-928</pages><issn>0270-4137</issn><issn>1097-0045</issn><eissn>1097-0045</eissn><abstract>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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30908670</pmid><doi>10.1002/pros.23797</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1916-7738</orcidid></addata></record> |
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| subjects | Biopsy Biopsy, Large-Core Needle - methods Cancer surgery Copy number diagnostic biopsy DNA, Neoplasm - genetics Formaldehyde Genetic Heterogeneity genomic heterogeneity Humans Male Medicin och hälsovetenskap multifocal tumors Mutation Nucleotide sequence Paraffin pathology Prostate cancer Prostatectomy Prostatic Neoplasms - diagnosis Prostatic Neoplasms - genetics Prostatic Neoplasms - pathology Tumors Urological surgery |
| title | Somatic alterations detected in diagnostic prostate biopsies provide an inadequate representation of multifocal prostate cancer |
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