Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma
Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and a...
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| Veröffentlicht in: | Cancers 2022-01, Vol.14 (2), p.421 |
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| creator | Alaña, Lide Nunes-Xavier, Caroline E Zaldumbide, Laura Martin-Guerrero, Idoia Mosteiro, Lorena Alba-Pavón, Piedad Villate, Olatz García-Obregón, Susana González-García, Hermenegildo Herraiz, Raquel Astigarraga, Itziar Pulido, Rafael García-Ariza, Miguel |
| description | Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3
mutations and were immunostained for nuclear β-catenin. One novel heterozygous
mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis. |
| doi_str_mv | 10.3390/cancers14020421 |
| format | Article |
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mutations and were immunostained for nuclear β-catenin. One novel heterozygous
mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14020421</identifier><identifier>PMID: 35053583</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Central nervous system ; Chromosomes ; Classification ; Clinical trials ; CTNNB1 gene ; DNA methylation ; Gene deletion ; Gene expression ; Genomes ; Histology ; LEF protein ; Medical prognosis ; Medulloblastoma ; Mutation ; Osteosarcoma ; Osteosarcoma cells ; Patients ; Pediatrics ; Plasmids ; Proteins ; Transcription ; Tumorigenesis ; Tumors ; Wnt protein ; β-Catenin</subject><ispartof>Cancers, 2022-01, Vol.14 (2), p.421</ispartof><rights>2022 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>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-f98bfa9f4674cf6f88ce1f2e3103772fe695148e00c969d9700082e08b9e33cb3</citedby><cites>FETCH-LOGICAL-c421t-f98bfa9f4674cf6f88ce1f2e3103772fe695148e00c969d9700082e08b9e33cb3</cites><orcidid>0000-0003-4768-094X ; 0000-0001-5203-9191 ; 0000-0002-8193-0773 ; 0000-0002-8102-5597 ; 0000-0002-0098-1908 ; 0000-0002-1875-6645 ; 0000-0001-9100-248X ; 0000-0001-8245-8944</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/PMC8773623/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773623/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35053583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alaña, Lide</creatorcontrib><creatorcontrib>Nunes-Xavier, Caroline E</creatorcontrib><creatorcontrib>Zaldumbide, Laura</creatorcontrib><creatorcontrib>Martin-Guerrero, Idoia</creatorcontrib><creatorcontrib>Mosteiro, Lorena</creatorcontrib><creatorcontrib>Alba-Pavón, Piedad</creatorcontrib><creatorcontrib>Villate, Olatz</creatorcontrib><creatorcontrib>García-Obregón, Susana</creatorcontrib><creatorcontrib>González-García, Hermenegildo</creatorcontrib><creatorcontrib>Herraiz, Raquel</creatorcontrib><creatorcontrib>Astigarraga, Itziar</creatorcontrib><creatorcontrib>Pulido, Rafael</creatorcontrib><creatorcontrib>García-Ariza, Miguel</creatorcontrib><title>Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3
mutations and were immunostained for nuclear β-catenin. One novel heterozygous
mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis.</description><subject>Antibodies</subject><subject>Central nervous system</subject><subject>Chromosomes</subject><subject>Classification</subject><subject>Clinical trials</subject><subject>CTNNB1 gene</subject><subject>DNA methylation</subject><subject>Gene deletion</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Histology</subject><subject>LEF protein</subject><subject>Medical prognosis</subject><subject>Medulloblastoma</subject><subject>Mutation</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma cells</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Transcription</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Wnt protein</subject><subject>β-Catenin</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</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>eNpdkUtPGzEUhS3UiqCUNTtkqZtuAn7M-LGpRKPykCBlQbe1PJ7r1sgZU3sGKf--hgBK8cK-lr97dI8PQkeUnHCuyamzg4NcaEMYaRjdQweMSLYQQjcfduoZOizlntTFOZVC7qMZb0nLW8UP0K-rHoYx-ODsGNKA7dDj82lwTxcb8VndNiUUnDy2eJUeIeLl3Wr1jeKbady2hAHfQh_smIPDN9BPMaYu2jKmtf2EPnobCxy-nHP08_z73fJycf3j4mp5dr1wdfBx4bXqvNW-EbJxXnilHFDPgFPCpWQehG5po4AQp4XutaxmFAOiOg2cu47P0det7sPUraF31VO20TzksLZ5Y5IN5v-XIfwxv9OjUVJywXgV-PIikNPfCcpo1qE4iNEOkKZimGCMKdkSWdHP79D7NOX6Uc8UZVIR3lbqdEu5nErJ4N-GocQ8xWfexVc7jnc9vPGvYfF_qq2XGw</recordid><startdate>20220114</startdate><enddate>20220114</enddate><creator>Alaña, Lide</creator><creator>Nunes-Xavier, Caroline E</creator><creator>Zaldumbide, Laura</creator><creator>Martin-Guerrero, Idoia</creator><creator>Mosteiro, Lorena</creator><creator>Alba-Pavón, Piedad</creator><creator>Villate, Olatz</creator><creator>García-Obregón, Susana</creator><creator>González-García, Hermenegildo</creator><creator>Herraiz, Raquel</creator><creator>Astigarraga, Itziar</creator><creator>Pulido, Rafael</creator><creator>García-Ariza, Miguel</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><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/0000-0003-4768-094X</orcidid><orcidid>https://orcid.org/0000-0001-5203-9191</orcidid><orcidid>https://orcid.org/0000-0002-8193-0773</orcidid><orcidid>https://orcid.org/0000-0002-8102-5597</orcidid><orcidid>https://orcid.org/0000-0002-0098-1908</orcidid><orcidid>https://orcid.org/0000-0002-1875-6645</orcidid><orcidid>https://orcid.org/0000-0001-9100-248X</orcidid><orcidid>https://orcid.org/0000-0001-8245-8944</orcidid></search><sort><creationdate>20220114</creationdate><title>Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma</title><author>Alaña, Lide ; 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We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3
mutations and were immunostained for nuclear β-catenin. One novel heterozygous
mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35053583</pmid><doi>10.3390/cancers14020421</doi><orcidid>https://orcid.org/0000-0003-4768-094X</orcidid><orcidid>https://orcid.org/0000-0001-5203-9191</orcidid><orcidid>https://orcid.org/0000-0002-8193-0773</orcidid><orcidid>https://orcid.org/0000-0002-8102-5597</orcidid><orcidid>https://orcid.org/0000-0002-0098-1908</orcidid><orcidid>https://orcid.org/0000-0002-1875-6645</orcidid><orcidid>https://orcid.org/0000-0001-9100-248X</orcidid><orcidid>https://orcid.org/0000-0001-8245-8944</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Antibodies Central nervous system Chromosomes Classification Clinical trials CTNNB1 gene DNA methylation Gene deletion Gene expression Genomes Histology LEF protein Medical prognosis Medulloblastoma Mutation Osteosarcoma Osteosarcoma cells Patients Pediatrics Plasmids Proteins Transcription Tumorigenesis Tumors Wnt protein β-Catenin |
| title | Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma |
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