Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions
GNAS (guanine nucleotide-binding protein/ α -subunit) mutations that induce the activation of G-protein α -subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of GNAS mutations in fibrous dysplasia and other fibro-osseou...
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| Veröffentlicht in: | Modern pathology 2013-07, Vol.26 (7), p.911-921 |
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| creator | Tabareau-Delalande, Flore Collin, Christine Gomez-Brouchet, Anne Decouvelaere, Anne-Valérie Bouvier, Corinne Larousserie, Frédérique Marie, Béatrice Delfour, Christophe Aubert, Sébastien Rosset, Philippe de Muret, Anne Pagès, Jean-Christophe de Pinieux, Gonzague |
| description | GNAS
(guanine nucleotide-binding protein/
α
-subunit) mutations that induce the activation of G-protein
α
-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of
GNAS
mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia.
GNAS
mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the
GNAS
mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9).
GNAS
mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%,
P
=0.96), regardless of sex (
P
=0.44), age (
P
=0.90) and location (
P
=1).
GNAS
mutations were not detected in any other fibro-osseous lesions. The
GNAS
mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of
GNAS
mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia. |
| doi_str_mv | 10.1038/modpathol.2012.223 |
| format | Article |
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(guanine nucleotide-binding protein/
α
-subunit) mutations that induce the activation of G-protein
α
-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of
GNAS
mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia.
GNAS
mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the
GNAS
mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9).
GNAS
mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%,
P
=0.96), regardless of sex (
P
=0.44), age (
P
=0.90) and location (
P
=1).
GNAS
mutations were not detected in any other fibro-osseous lesions. The
GNAS
mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of
GNAS
mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2012.223</identifier><identifier>PMID: 23370769</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/737 ; 692/699/67/1344 ; 692/700/139/422 ; Adolescent ; Adult ; Biomarkers - analysis ; Bone cancer ; Bone Diseases, Developmental - genetics ; Bone Neoplasms - genetics ; Child ; Chromogranins ; DNA Mutational Analysis ; Female ; Fibroma, Ossifying - genetics ; GTP-Binding Protein alpha Subunits, Gs - genetics ; Humans ; Laboratory Medicine ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; original-article ; Osteosarcoma - genetics ; Pathology ; Proteins ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Stem cells ; Young Adult</subject><ispartof>Modern pathology, 2013-07, Vol.26 (7), p.911-921</ispartof><rights>United States & Canadian Academy of Pathology 2013</rights><rights>Copyright Nature Publishing Group Jul 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-a826eb57c81ff282e11c1ab545fd9494113d49435a7cc7f7d639eeecfcc5a9033</citedby><cites>FETCH-LOGICAL-c518t-a826eb57c81ff282e11c1ab545fd9494113d49435a7cc7f7d639eeecfcc5a9033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23370769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tabareau-Delalande, Flore</creatorcontrib><creatorcontrib>Collin, Christine</creatorcontrib><creatorcontrib>Gomez-Brouchet, Anne</creatorcontrib><creatorcontrib>Decouvelaere, Anne-Valérie</creatorcontrib><creatorcontrib>Bouvier, Corinne</creatorcontrib><creatorcontrib>Larousserie, Frédérique</creatorcontrib><creatorcontrib>Marie, Béatrice</creatorcontrib><creatorcontrib>Delfour, Christophe</creatorcontrib><creatorcontrib>Aubert, Sébastien</creatorcontrib><creatorcontrib>Rosset, Philippe</creatorcontrib><creatorcontrib>de Muret, Anne</creatorcontrib><creatorcontrib>Pagès, Jean-Christophe</creatorcontrib><creatorcontrib>de Pinieux, Gonzague</creatorcontrib><title>Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>GNAS
(guanine nucleotide-binding protein/
α
-subunit) mutations that induce the activation of G-protein
α
-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of
GNAS
mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia.
GNAS
mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the
GNAS
mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9).
GNAS
mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%,
P
=0.96), regardless of sex (
P
=0.44), age (
P
=0.90) and location (
P
=1).
GNAS
mutations were not detected in any other fibro-osseous lesions. The
GNAS
mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of
GNAS
mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.</description><subject>631/208/737</subject><subject>692/699/67/1344</subject><subject>692/700/139/422</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Biomarkers - analysis</subject><subject>Bone cancer</subject><subject>Bone Diseases, Developmental - genetics</subject><subject>Bone Neoplasms - genetics</subject><subject>Child</subject><subject>Chromogranins</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Fibroma, Ossifying - genetics</subject><subject>GTP-Binding Protein alpha Subunits, Gs - genetics</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>original-article</subject><subject>Osteosarcoma - genetics</subject><subject>Pathology</subject><subject>Proteins</subject><subject>Retrospective Studies</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sensitivity and Specificity</subject><subject>Stem cells</subject><subject>Young Adult</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1u1DAUhS0EotPCC7BAltiwyeCfeGKzq1pakCpYAOvI41xPXSVx8HVGmvfhQXGYUiEEYnVt3-8c2_cQ8oKzNWdSvxliN9l8G_u1YFyshZCPyIorySomtHpMVkwbWUmjxAk5RbxjjNdKi6fkREjZsGZjVuT7ZbC7MWIOju5tPwONnoZxD-VkZ3MYd_T64_lnOsy57OKIpUl92KZYRUSIM9IecGm8pZYmyCniBC6HPVDMc3dY_AynziLgsv6pLarugFNvMVhqx47WjMZ8C-nv1s_IE297hOf39Yx8vXr35eJ9dfPp-sPF-U3lFNe5slpsYKsap7n3Qgvg3HG7VbXynalNzbnsSpHKNs41vuk20gCA884pa5iUZ-T10XdK8dtcRtAOAR30vR2X57S85kKxMmH9f1Q2sq5LDLygr_5A7-KcxvKRhRKN5MyIQokj5coEMYFvpxQGmw4tZ-0Sd_sQd7vE3Za4i-jlvfW8HaB7kPzKtwDyCGBpjTtIv939b9sflG28IQ</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Tabareau-Delalande, Flore</creator><creator>Collin, Christine</creator><creator>Gomez-Brouchet, Anne</creator><creator>Decouvelaere, Anne-Valérie</creator><creator>Bouvier, Corinne</creator><creator>Larousserie, Frédérique</creator><creator>Marie, Béatrice</creator><creator>Delfour, Christophe</creator><creator>Aubert, Sébastien</creator><creator>Rosset, Philippe</creator><creator>de Muret, Anne</creator><creator>Pagès, Jean-Christophe</creator><creator>de Pinieux, Gonzague</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</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>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20130701</creationdate><title>Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions</title><author>Tabareau-Delalande, Flore ; Collin, Christine ; Gomez-Brouchet, Anne ; Decouvelaere, Anne-Valérie ; Bouvier, Corinne ; Larousserie, Frédérique ; Marie, Béatrice ; Delfour, Christophe ; Aubert, Sébastien ; Rosset, Philippe ; de Muret, Anne ; Pagès, Jean-Christophe ; de Pinieux, Gonzague</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-a826eb57c81ff282e11c1ab545fd9494113d49435a7cc7f7d639eeecfcc5a9033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/208/737</topic><topic>692/699/67/1344</topic><topic>692/700/139/422</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Biomarkers - analysis</topic><topic>Bone cancer</topic><topic>Bone Diseases, Developmental - genetics</topic><topic>Bone Neoplasms - genetics</topic><topic>Child</topic><topic>Chromogranins</topic><topic>DNA Mutational Analysis</topic><topic>Female</topic><topic>Fibroma, Ossifying - genetics</topic><topic>GTP-Binding Protein alpha Subunits, Gs - genetics</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>original-article</topic><topic>Osteosarcoma - genetics</topic><topic>Pathology</topic><topic>Proteins</topic><topic>Retrospective Studies</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sensitivity and Specificity</topic><topic>Stem cells</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tabareau-Delalande, Flore</creatorcontrib><creatorcontrib>Collin, Christine</creatorcontrib><creatorcontrib>Gomez-Brouchet, Anne</creatorcontrib><creatorcontrib>Decouvelaere, Anne-Valérie</creatorcontrib><creatorcontrib>Bouvier, Corinne</creatorcontrib><creatorcontrib>Larousserie, Frédérique</creatorcontrib><creatorcontrib>Marie, Béatrice</creatorcontrib><creatorcontrib>Delfour, Christophe</creatorcontrib><creatorcontrib>Aubert, Sébastien</creatorcontrib><creatorcontrib>Rosset, Philippe</creatorcontrib><creatorcontrib>de Muret, Anne</creatorcontrib><creatorcontrib>Pagès, Jean-Christophe</creatorcontrib><creatorcontrib>de Pinieux, Gonzague</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>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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>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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tabareau-Delalande, Flore</au><au>Collin, Christine</au><au>Gomez-Brouchet, Anne</au><au>Decouvelaere, Anne-Valérie</au><au>Bouvier, Corinne</au><au>Larousserie, Frédérique</au><au>Marie, Béatrice</au><au>Delfour, Christophe</au><au>Aubert, Sébastien</au><au>Rosset, Philippe</au><au>de Muret, Anne</au><au>Pagès, Jean-Christophe</au><au>de Pinieux, Gonzague</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>26</volume><issue>7</issue><spage>911</spage><epage>921</epage><pages>911-921</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>GNAS
(guanine nucleotide-binding protein/
α
-subunit) mutations that induce the activation of G-protein
α
-subunit participate in the pathogenesis of fibrous dysplasia. The aim of this study was to evaluate the sensitivity and specificity of
GNAS
mutations in fibrous dysplasia and other fibro-osseous lesions, to assess the value of investigating this mutation in the diagnosis of fibro-osseous lesions. We studied 91 cases of fibrous dysplasia. The quality and/or quantity of genomic DNA were suitable for molecular analysis for 51 cases of fibrous dysplasia.
GNAS
mutations were investigated by three techniques: high-resolution melting (exon 8), allele-specific PCR (exons 8 and 9) and/or direct DNA sequencing (exons 8 and 9). Fibrous dysplasia samples were classified blind to the
GNAS
mutation status into six histological subtypes as conventional, fibro-involutive, osteosclerosing, cementifying, osteocartilaginous and with prominent aneurysmal cystic changes. We also studied 14 cases of low-grade osteosarcoma, 21 cases of ossifying fibroma, 3 cases of osteofibrous dysplasia, 1 case of osseous dysplasia of the jawbone and 1 post-traumatic lesion of the ribs. Twenty-three cases of fibrous dysplasia (45%) showed mutations of codon 201 (exon 8, p.R201H or p.R201C). No mutation was found on codon 227 (exon 9).
GNAS
mutations in conventional fibrous dysplasia were detected in the same proportion (47%) as in the other histological subtypes (47%,
P
=0.96), regardless of sex (
P
=0.44), age (
P
=0.90) and location (
P
=1).
GNAS
mutations were not detected in any other fibro-osseous lesions. The
GNAS
mutation was thus specific to fibrous dysplasia in the context of fibro-osseous lesions. The particular mosaicism of mutant and non-mutant cells within the lesion or the existence of other mutations not already described could explain the lack of
GNAS
mutation in cases of fibrous dysplasia. Investigating this mutation may constitute a valuable complementary diagnostic tool, despite its low sensitivity, particularly in unconventional morphologically different subtypes of fibrous dysplasia.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23370769</pmid><doi>10.1038/modpathol.2012.223</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Modern pathology, 2013-07, Vol.26 (7), p.911-921 |
| issn | 0893-3952 1530-0285 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 631/208/737 692/699/67/1344 692/700/139/422 Adolescent Adult Biomarkers - analysis Bone cancer Bone Diseases, Developmental - genetics Bone Neoplasms - genetics Child Chromogranins DNA Mutational Analysis Female Fibroma, Ossifying - genetics GTP-Binding Protein alpha Subunits, Gs - genetics Humans Laboratory Medicine Male Medicine Medicine & Public Health Middle Aged Mutation original-article Osteosarcoma - genetics Pathology Proteins Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction Sensitivity and Specificity Stem cells Young Adult |
| title | Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions |
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