Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions
Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to...
Gespeichert in:
| Veröffentlicht in: | Cancers 2021-06, Vol.13 (13), p.3119 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 13 |
| container_start_page | 3119 |
| container_title | Cancers |
| container_volume | 13 |
| creator | Lawlor, Rita T. Mattiolo, Paola Mafficini, Andrea Hong, Seung-Mo Piredda, Maria L. Taormina, Sergio V. Malleo, Giuseppe Marchegiani, Giovanni Pea, Antonio Salvia, Roberto Kryklyva, Valentyna Shin, Jae Il Brosens, Lodewijk A. Milella, Michele Scarpa, Aldo Luchini, Claudio |
| description | Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer. |
| doi_str_mv | 10.3390/cancers13133119 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8269341</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2548400638</sourcerecordid><originalsourceid>FETCH-LOGICAL-c464t-24fc650cca444082dac13e2ce2e8ab2776573c07f727d8e1a05d8523afd638473</originalsourceid><addsrcrecordid>eNpdkc1v1DAQxS0EolXpmaslLlxC_e2EAxKs-KhU1ELL2Zo6E-qS2IudFO25_3i92wpBfbE1_um9NzOEvOTsjZQdO_IQPebCJZeS8-4J2RfMisaYTj39571HDku5ZvVUzBr7nOxJJZjRWu2T24tlSpl-XWaYQ4ow0g9L7jFSKBToWZoxzmFbDWmC_AszHSp-PE1LTPMVZlhvaIj0rEbJWCU8Xe1SvaXnmzLjtCt9x5uAfyjEnp7PYRyb03V1-LZg2XqWF-TZAGPBw4f7gPz49PFi9aU5Of18vHp_0nhl1NwINXijmfeglGKt6MFzicKjwBYuhbVGW-mZHaywfYscmO5bLSQMvZGtsvKAvLvXXS-XE_a-tpZhdOscamsblyC4_39iuHI_041rhemk4lXg9YNATr-36d0UisdxhIhpKU5o1SrGqltFXz1Cr9OS63x3VCds12ldqaN7yudUSsbhbxjO3HbH7tGO5R0UtJvG</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2549279955</pqid></control><display><type>article</type><title>Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Lawlor, Rita T. ; Mattiolo, Paola ; Mafficini, Andrea ; Hong, Seung-Mo ; Piredda, Maria L. ; Taormina, Sergio V. ; Malleo, Giuseppe ; Marchegiani, Giovanni ; Pea, Antonio ; Salvia, Roberto ; Kryklyva, Valentyna ; Shin, Jae Il ; Brosens, Lodewijk A. ; Milella, Michele ; Scarpa, Aldo ; Luchini, Claudio</creator><creatorcontrib>Lawlor, Rita T. ; Mattiolo, Paola ; Mafficini, Andrea ; Hong, Seung-Mo ; Piredda, Maria L. ; Taormina, Sergio V. ; Malleo, Giuseppe ; Marchegiani, Giovanni ; Pea, Antonio ; Salvia, Roberto ; Kryklyva, Valentyna ; Shin, Jae Il ; Brosens, Lodewijk A. ; Milella, Michele ; Scarpa, Aldo ; Luchini, Claudio</creatorcontrib><description>Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13133119</identifier><identifier>PMID: 34206554</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Adenocarcinoma ; Biomarkers ; Immunotherapy ; Microsatellite instability ; Mismatch repair ; Mutation ; Next-generation sequencing ; Pancreatic cancer ; Review ; Tumor cells ; Tumors</subject><ispartof>Cancers, 2021-06, Vol.13 (13), p.3119</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-24fc650cca444082dac13e2ce2e8ab2776573c07f727d8e1a05d8523afd638473</citedby><cites>FETCH-LOGICAL-c464t-24fc650cca444082dac13e2ce2e8ab2776573c07f727d8e1a05d8523afd638473</cites><orcidid>0000-0003-1678-739X ; 0000-0002-7471-3121 ; 0000-0003-4901-4908 ; 0000-0003-3160-0634 ; 0000-0002-3514-8473 ; 0000-0002-6824-4533 ; 0000-0003-2326-1820 ; 0000-0002-5601-0879</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269341/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269341/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Lawlor, Rita T.</creatorcontrib><creatorcontrib>Mattiolo, Paola</creatorcontrib><creatorcontrib>Mafficini, Andrea</creatorcontrib><creatorcontrib>Hong, Seung-Mo</creatorcontrib><creatorcontrib>Piredda, Maria L.</creatorcontrib><creatorcontrib>Taormina, Sergio V.</creatorcontrib><creatorcontrib>Malleo, Giuseppe</creatorcontrib><creatorcontrib>Marchegiani, Giovanni</creatorcontrib><creatorcontrib>Pea, Antonio</creatorcontrib><creatorcontrib>Salvia, Roberto</creatorcontrib><creatorcontrib>Kryklyva, Valentyna</creatorcontrib><creatorcontrib>Shin, Jae Il</creatorcontrib><creatorcontrib>Brosens, Lodewijk A.</creatorcontrib><creatorcontrib>Milella, Michele</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Luchini, Claudio</creatorcontrib><title>Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions</title><title>Cancers</title><description>Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.</description><subject>Adenocarcinoma</subject><subject>Biomarkers</subject><subject>Immunotherapy</subject><subject>Microsatellite instability</subject><subject>Mismatch repair</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Pancreatic cancer</subject><subject>Review</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1v1DAQxS0EolXpmaslLlxC_e2EAxKs-KhU1ELL2Zo6E-qS2IudFO25_3i92wpBfbE1_um9NzOEvOTsjZQdO_IQPebCJZeS8-4J2RfMisaYTj39571HDku5ZvVUzBr7nOxJJZjRWu2T24tlSpl-XWaYQ4ow0g9L7jFSKBToWZoxzmFbDWmC_AszHSp-PE1LTPMVZlhvaIj0rEbJWCU8Xe1SvaXnmzLjtCt9x5uAfyjEnp7PYRyb03V1-LZg2XqWF-TZAGPBw4f7gPz49PFi9aU5Of18vHp_0nhl1NwINXijmfeglGKt6MFzicKjwBYuhbVGW-mZHaywfYscmO5bLSQMvZGtsvKAvLvXXS-XE_a-tpZhdOscamsblyC4_39iuHI_041rhemk4lXg9YNATr-36d0UisdxhIhpKU5o1SrGqltFXz1Cr9OS63x3VCds12ldqaN7yudUSsbhbxjO3HbH7tGO5R0UtJvG</recordid><startdate>20210622</startdate><enddate>20210622</enddate><creator>Lawlor, Rita T.</creator><creator>Mattiolo, Paola</creator><creator>Mafficini, Andrea</creator><creator>Hong, Seung-Mo</creator><creator>Piredda, Maria L.</creator><creator>Taormina, Sergio V.</creator><creator>Malleo, Giuseppe</creator><creator>Marchegiani, Giovanni</creator><creator>Pea, Antonio</creator><creator>Salvia, Roberto</creator><creator>Kryklyva, Valentyna</creator><creator>Shin, Jae Il</creator><creator>Brosens, Lodewijk A.</creator><creator>Milella, Michele</creator><creator>Scarpa, Aldo</creator><creator>Luchini, Claudio</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1678-739X</orcidid><orcidid>https://orcid.org/0000-0002-7471-3121</orcidid><orcidid>https://orcid.org/0000-0003-4901-4908</orcidid><orcidid>https://orcid.org/0000-0003-3160-0634</orcidid><orcidid>https://orcid.org/0000-0002-3514-8473</orcidid><orcidid>https://orcid.org/0000-0002-6824-4533</orcidid><orcidid>https://orcid.org/0000-0003-2326-1820</orcidid><orcidid>https://orcid.org/0000-0002-5601-0879</orcidid></search><sort><creationdate>20210622</creationdate><title>Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions</title><author>Lawlor, Rita T. ; Mattiolo, Paola ; Mafficini, Andrea ; Hong, Seung-Mo ; Piredda, Maria L. ; Taormina, Sergio V. ; Malleo, Giuseppe ; Marchegiani, Giovanni ; Pea, Antonio ; Salvia, Roberto ; Kryklyva, Valentyna ; Shin, Jae Il ; Brosens, Lodewijk A. ; Milella, Michele ; Scarpa, Aldo ; Luchini, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-24fc650cca444082dac13e2ce2e8ab2776573c07f727d8e1a05d8523afd638473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Biomarkers</topic><topic>Immunotherapy</topic><topic>Microsatellite instability</topic><topic>Mismatch repair</topic><topic>Mutation</topic><topic>Next-generation sequencing</topic><topic>Pancreatic cancer</topic><topic>Review</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lawlor, Rita T.</creatorcontrib><creatorcontrib>Mattiolo, Paola</creatorcontrib><creatorcontrib>Mafficini, Andrea</creatorcontrib><creatorcontrib>Hong, Seung-Mo</creatorcontrib><creatorcontrib>Piredda, Maria L.</creatorcontrib><creatorcontrib>Taormina, Sergio V.</creatorcontrib><creatorcontrib>Malleo, Giuseppe</creatorcontrib><creatorcontrib>Marchegiani, Giovanni</creatorcontrib><creatorcontrib>Pea, Antonio</creatorcontrib><creatorcontrib>Salvia, Roberto</creatorcontrib><creatorcontrib>Kryklyva, Valentyna</creatorcontrib><creatorcontrib>Shin, Jae Il</creatorcontrib><creatorcontrib>Brosens, Lodewijk A.</creatorcontrib><creatorcontrib>Milella, Michele</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Luchini, Claudio</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lawlor, Rita T.</au><au>Mattiolo, Paola</au><au>Mafficini, Andrea</au><au>Hong, Seung-Mo</au><au>Piredda, Maria L.</au><au>Taormina, Sergio V.</au><au>Malleo, Giuseppe</au><au>Marchegiani, Giovanni</au><au>Pea, Antonio</au><au>Salvia, Roberto</au><au>Kryklyva, Valentyna</au><au>Shin, Jae Il</au><au>Brosens, Lodewijk A.</au><au>Milella, Michele</au><au>Scarpa, Aldo</au><au>Luchini, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions</atitle><jtitle>Cancers</jtitle><date>2021-06-22</date><risdate>2021</risdate><volume>13</volume><issue>13</issue><spage>3119</spage><pages>3119-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology (p < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34206554</pmid><doi>10.3390/cancers13133119</doi><orcidid>https://orcid.org/0000-0003-1678-739X</orcidid><orcidid>https://orcid.org/0000-0002-7471-3121</orcidid><orcidid>https://orcid.org/0000-0003-4901-4908</orcidid><orcidid>https://orcid.org/0000-0003-3160-0634</orcidid><orcidid>https://orcid.org/0000-0002-3514-8473</orcidid><orcidid>https://orcid.org/0000-0002-6824-4533</orcidid><orcidid>https://orcid.org/0000-0003-2326-1820</orcidid><orcidid>https://orcid.org/0000-0002-5601-0879</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2021-06, Vol.13 (13), p.3119 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8269341 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Adenocarcinoma Biomarkers Immunotherapy Microsatellite instability Mismatch repair Mutation Next-generation sequencing Pancreatic cancer Review Tumor cells Tumors |
| title | Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T17%3A00%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tumor%20Mutational%20Burden%20as%20a%20Potential%20Biomarker%20for%20Immunotherapy%20in%20Pancreatic%20Cancer:%20Systematic%20Review%20and%20Still-Open%20Questions&rft.jtitle=Cancers&rft.au=Lawlor,%20Rita%20T.&rft.date=2021-06-22&rft.volume=13&rft.issue=13&rft.spage=3119&rft.pages=3119-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers13133119&rft_dat=%3Cproquest_pubme%3E2548400638%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2549279955&rft_id=info:pmid/34206554&rfr_iscdi=true |