A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping
Background Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized pa...
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| Veröffentlicht in: | Targeted oncology 2020-12, Vol.15 (6), p.759-771 |
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| creator | Louveau, Baptiste Jouenne, Fanélie Têtu, Pauline Sadoux, Aurélie Gruber, Aurélia Lopes, Eddie Delyon, Julie Serror, Kevin Marco, Oren Da Meda, Laetitia Ndiaye, Aminata Lermine, Alban Dumaz, Nicolas Battistella, Maxime Baroudjian, Barouyr Lebbe, Céleste Mourah, Samia |
| description | Background
Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.
Objective
The objective of this study was to present such a customized next-generation sequencing panel in melanoma.
Methods
Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.
Results
Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with
BRAF
,
NRAS
,
CDKN2A
,
CCND1
, and
MET
as the most frequently altered genes. Among patients with
BRAF
V600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with
RAS
hotspot mutated lesions and in patients with neither
BRAF
V600 nor
RAS
hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.
Conclusions
Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients’ clinical management. |
| doi_str_mv | 10.1007/s11523-020-00764-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_inserm_03033434v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2473254347</sourcerecordid><originalsourceid>FETCH-LOGICAL-c412t-43336281d6b05a550940e745e946a05338416884454fe7727447f5096840dd13</originalsourceid><addsrcrecordid>eNp9kU9v1DAQxSNERUvhC3BAlrhwINR_xnFyXK2grbS0CPbAzXI3s11Xib3YSWGPfHNmSbtIHDjZ4_n5zbNfUbwS_L3g3JxlIbRUJZe8pLKCEp4UJ8KYqpQV__b0ca-b6rh4nvMd52Ck5s-KY6WEFlScFL9m7BN2LsTelUvnu5iwZVf4cyjPMWByg4-BfcXvI4aVD7fsswvYsXkctx2BP_ywYY7KfptwgyH7e2Sz4Lpd9pkNkV1SI9LZlzgOPuBhFiP1OOy2JPmiOFq7LuPLh_W0WH78sJxflIvr88v5bFGuQMihBKVUJWvRVjdcO615AxwNaGygclwrVYOo6hpAwxqNkQbArImqauBtK9Rp8W6S3bjObpPvXdrZ6Ly9mC2sDxlTb7niSoGC-z3-dsLJPz0-D7b3eYUd2cc4ZitBm8YI3QChb_5B7-KY6BP2lFFSk6IhSk7UKsWcE64PJgS3-zjtFKelOO2fOO1e-vWD9HjTY3u48pgfAWoCMrXCLaa_s_8j-xugYqil</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473254347</pqid></control><display><type>article</type><title>A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Louveau, Baptiste ; Jouenne, Fanélie ; Têtu, Pauline ; Sadoux, Aurélie ; Gruber, Aurélia ; Lopes, Eddie ; Delyon, Julie ; Serror, Kevin ; Marco, Oren ; Da Meda, Laetitia ; Ndiaye, Aminata ; Lermine, Alban ; Dumaz, Nicolas ; Battistella, Maxime ; Baroudjian, Barouyr ; Lebbe, Céleste ; Mourah, Samia</creator><creatorcontrib>Louveau, Baptiste ; Jouenne, Fanélie ; Têtu, Pauline ; Sadoux, Aurélie ; Gruber, Aurélia ; Lopes, Eddie ; Delyon, Julie ; Serror, Kevin ; Marco, Oren ; Da Meda, Laetitia ; Ndiaye, Aminata ; Lermine, Alban ; Dumaz, Nicolas ; Battistella, Maxime ; Baroudjian, Barouyr ; Lebbe, Céleste ; Mourah, Samia</creatorcontrib><description>Background
Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.
Objective
The objective of this study was to present such a customized next-generation sequencing panel in melanoma.
Methods
Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.
Results
Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with
BRAF
,
NRAS
,
CDKN2A
,
CCND1
, and
MET
as the most frequently altered genes. Among patients with
BRAF
V600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with
RAS
hotspot mutated lesions and in patients with neither
BRAF
V600 nor
RAS
hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.
Conclusions
Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients’ clinical management.</description><identifier>ISSN: 1776-2596</identifier><identifier>EISSN: 1776-260X</identifier><identifier>DOI: 10.1007/s11523-020-00764-4</identifier><identifier>PMID: 33151472</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Biochemistry, Molecular Biology ; Biomedicine ; Cancer ; Dermatology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing - methods ; Human health and pathology ; Humans ; Kinases ; Life Sciences ; Male ; Medicine ; Medicine & Public Health ; Melanoma ; Melanoma - genetics ; Melanoma - pathology ; Molecular Networks ; Mutation ; Oncology ; Original Research Article ; Structural Biology ; Treatment resistance</subject><ispartof>Targeted oncology, 2020-12, Vol.15 (6), p.759-771</ispartof><rights>Springer Nature Switzerland AG 2020</rights><rights>Springer Nature Switzerland AG 2020.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-43336281d6b05a550940e745e946a05338416884454fe7727447f5096840dd13</citedby><cites>FETCH-LOGICAL-c412t-43336281d6b05a550940e745e946a05338416884454fe7727447f5096840dd13</cites><orcidid>0000-0003-2988-6792 ; 0000-0002-4557-3377 ; 0000-0002-5854-7290 ; 0000-0002-7053-7431</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11523-020-00764-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11523-020-00764-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33151472$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03033434$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Louveau, Baptiste</creatorcontrib><creatorcontrib>Jouenne, Fanélie</creatorcontrib><creatorcontrib>Têtu, Pauline</creatorcontrib><creatorcontrib>Sadoux, Aurélie</creatorcontrib><creatorcontrib>Gruber, Aurélia</creatorcontrib><creatorcontrib>Lopes, Eddie</creatorcontrib><creatorcontrib>Delyon, Julie</creatorcontrib><creatorcontrib>Serror, Kevin</creatorcontrib><creatorcontrib>Marco, Oren</creatorcontrib><creatorcontrib>Da Meda, Laetitia</creatorcontrib><creatorcontrib>Ndiaye, Aminata</creatorcontrib><creatorcontrib>Lermine, Alban</creatorcontrib><creatorcontrib>Dumaz, Nicolas</creatorcontrib><creatorcontrib>Battistella, Maxime</creatorcontrib><creatorcontrib>Baroudjian, Barouyr</creatorcontrib><creatorcontrib>Lebbe, Céleste</creatorcontrib><creatorcontrib>Mourah, Samia</creatorcontrib><title>A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping</title><title>Targeted oncology</title><addtitle>Targ Oncol</addtitle><addtitle>Target Oncol</addtitle><description>Background
Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.
Objective
The objective of this study was to present such a customized next-generation sequencing panel in melanoma.
Methods
Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.
Results
Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with
BRAF
,
NRAS
,
CDKN2A
,
CCND1
, and
MET
as the most frequently altered genes. Among patients with
BRAF
V600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with
RAS
hotspot mutated lesions and in patients with neither
BRAF
V600 nor
RAS
hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.
Conclusions
Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients’ clinical management.</description><subject>Biochemistry, Molecular Biology</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Dermatology</subject><subject>Female</subject><subject>Genotype</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melanoma</subject><subject>Melanoma - genetics</subject><subject>Melanoma - pathology</subject><subject>Molecular Networks</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Original Research Article</subject><subject>Structural Biology</subject><subject>Treatment resistance</subject><issn>1776-2596</issn><issn>1776-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU9v1DAQxSNERUvhC3BAlrhwINR_xnFyXK2grbS0CPbAzXI3s11Xib3YSWGPfHNmSbtIHDjZ4_n5zbNfUbwS_L3g3JxlIbRUJZe8pLKCEp4UJ8KYqpQV__b0ca-b6rh4nvMd52Ck5s-KY6WEFlScFL9m7BN2LsTelUvnu5iwZVf4cyjPMWByg4-BfcXvI4aVD7fsswvYsXkctx2BP_ywYY7KfptwgyH7e2Sz4Lpd9pkNkV1SI9LZlzgOPuBhFiP1OOy2JPmiOFq7LuPLh_W0WH78sJxflIvr88v5bFGuQMihBKVUJWvRVjdcO615AxwNaGygclwrVYOo6hpAwxqNkQbArImqauBtK9Rp8W6S3bjObpPvXdrZ6Ly9mC2sDxlTb7niSoGC-z3-dsLJPz0-D7b3eYUd2cc4ZitBm8YI3QChb_5B7-KY6BP2lFFSk6IhSk7UKsWcE64PJgS3-zjtFKelOO2fOO1e-vWD9HjTY3u48pgfAWoCMrXCLaa_s_8j-xugYqil</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Louveau, Baptiste</creator><creator>Jouenne, Fanélie</creator><creator>Têtu, Pauline</creator><creator>Sadoux, Aurélie</creator><creator>Gruber, Aurélia</creator><creator>Lopes, Eddie</creator><creator>Delyon, Julie</creator><creator>Serror, Kevin</creator><creator>Marco, Oren</creator><creator>Da Meda, Laetitia</creator><creator>Ndiaye, Aminata</creator><creator>Lermine, Alban</creator><creator>Dumaz, Nicolas</creator><creator>Battistella, Maxime</creator><creator>Baroudjian, Barouyr</creator><creator>Lebbe, Céleste</creator><creator>Mourah, Samia</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><general>Springer Verlag (Germany)</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-2988-6792</orcidid><orcidid>https://orcid.org/0000-0002-4557-3377</orcidid><orcidid>https://orcid.org/0000-0002-5854-7290</orcidid><orcidid>https://orcid.org/0000-0002-7053-7431</orcidid></search><sort><creationdate>20201201</creationdate><title>A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping</title><author>Louveau, Baptiste ; Jouenne, Fanélie ; Têtu, Pauline ; Sadoux, Aurélie ; Gruber, Aurélia ; Lopes, Eddie ; Delyon, Julie ; Serror, Kevin ; Marco, Oren ; Da Meda, Laetitia ; Ndiaye, Aminata ; Lermine, Alban ; Dumaz, Nicolas ; Battistella, Maxime ; Baroudjian, Barouyr ; Lebbe, Céleste ; Mourah, Samia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-43336281d6b05a550940e745e946a05338416884454fe7727447f5096840dd13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biochemistry, Molecular Biology</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Dermatology</topic><topic>Female</topic><topic>Genotype</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melanoma</topic><topic>Melanoma - genetics</topic><topic>Melanoma - pathology</topic><topic>Molecular Networks</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Original Research Article</topic><topic>Structural Biology</topic><topic>Treatment resistance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Louveau, Baptiste</creatorcontrib><creatorcontrib>Jouenne, Fanélie</creatorcontrib><creatorcontrib>Têtu, Pauline</creatorcontrib><creatorcontrib>Sadoux, Aurélie</creatorcontrib><creatorcontrib>Gruber, Aurélia</creatorcontrib><creatorcontrib>Lopes, Eddie</creatorcontrib><creatorcontrib>Delyon, Julie</creatorcontrib><creatorcontrib>Serror, Kevin</creatorcontrib><creatorcontrib>Marco, Oren</creatorcontrib><creatorcontrib>Da Meda, Laetitia</creatorcontrib><creatorcontrib>Ndiaye, Aminata</creatorcontrib><creatorcontrib>Lermine, Alban</creatorcontrib><creatorcontrib>Dumaz, Nicolas</creatorcontrib><creatorcontrib>Battistella, Maxime</creatorcontrib><creatorcontrib>Baroudjian, Barouyr</creatorcontrib><creatorcontrib>Lebbe, Céleste</creatorcontrib><creatorcontrib>Mourah, Samia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Targeted oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Louveau, Baptiste</au><au>Jouenne, Fanélie</au><au>Têtu, Pauline</au><au>Sadoux, Aurélie</au><au>Gruber, Aurélia</au><au>Lopes, Eddie</au><au>Delyon, Julie</au><au>Serror, Kevin</au><au>Marco, Oren</au><au>Da Meda, Laetitia</au><au>Ndiaye, Aminata</au><au>Lermine, Alban</au><au>Dumaz, Nicolas</au><au>Battistella, Maxime</au><au>Baroudjian, Barouyr</au><au>Lebbe, Céleste</au><au>Mourah, Samia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping</atitle><jtitle>Targeted oncology</jtitle><stitle>Targ Oncol</stitle><addtitle>Target Oncol</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>15</volume><issue>6</issue><spage>759</spage><epage>771</epage><pages>759-771</pages><issn>1776-2596</issn><eissn>1776-260X</eissn><abstract>Background
Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies.
Objective
The objective of this study was to present such a customized next-generation sequencing panel in melanoma.
Methods
Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations.
Results
Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with
BRAF
,
NRAS
,
CDKN2A
,
CCND1
, and
MET
as the most frequently altered genes. Among patients with
BRAF
V600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with
RAS
hotspot mutated lesions and in patients with neither
BRAF
V600 nor
RAS
hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively.
Conclusions
Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients’ clinical management.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>33151472</pmid><doi>10.1007/s11523-020-00764-4</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2988-6792</orcidid><orcidid>https://orcid.org/0000-0002-4557-3377</orcidid><orcidid>https://orcid.org/0000-0002-5854-7290</orcidid><orcidid>https://orcid.org/0000-0002-7053-7431</orcidid></addata></record> |
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| ispartof | Targeted oncology, 2020-12, Vol.15 (6), p.759-771 |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Biochemistry, Molecular Biology Biomedicine Cancer Dermatology Female Genotype High-Throughput Nucleotide Sequencing - methods Human health and pathology Humans Kinases Life Sciences Male Medicine Medicine & Public Health Melanoma Melanoma - genetics Melanoma - pathology Molecular Networks Mutation Oncology Original Research Article Structural Biology Treatment resistance |
| title | A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping |
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