Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome
PURPOSELi-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of c...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society of Clinical Oncology
2021-12-01
|
| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO.21.00097 |
| _version_ | 1818775214405713920 |
|---|---|
| author | Renata Lazari Sandoval Cibele Masotti Mariana Petaccia de Macedo Maurício Fernando Silva Almeida Ribeiro Ana Carolina Rathsam Leite Sibele Inacio Meireles Rodrigo Medeiros Bovolin Fernando Costa Santini Rodrigo Ramella Munhoz Denis Leonardo Fontes Jardim Artur Katz Anamaria Aranha Camargo Gustavo dos Santos Fernandes Maria Isabel Achatz |
| author_facet | Renata Lazari Sandoval Cibele Masotti Mariana Petaccia de Macedo Maurício Fernando Silva Almeida Ribeiro Ana Carolina Rathsam Leite Sibele Inacio Meireles Rodrigo Medeiros Bovolin Fernando Costa Santini Rodrigo Ramella Munhoz Denis Leonardo Fontes Jardim Artur Katz Anamaria Aranha Camargo Gustavo dos Santos Fernandes Maria Isabel Achatz |
| author_sort | Renata Lazari Sandoval |
| collection | DOAJ |
| description | PURPOSELi-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer.MATERIALS AND METHODSWe determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil.RESULTSThe TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria.CONCLUSIONThe identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation. |
| first_indexed | 2024-12-18T10:53:29Z |
| format | Article |
| id | doaj.art-6a8c6059217b4076af1e7479ce18af74 |
| institution | Directory Open Access Journal |
| issn | 2687-8941 |
| language | English |
| last_indexed | 2024-12-18T10:53:29Z |
| publishDate | 2021-12-01 |
| publisher | American Society of Clinical Oncology |
| record_format | Article |
| series | JCO Global Oncology |
| spelling | doaj.art-6a8c6059217b4076af1e7479ce18af742022-12-21T21:10:23ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412021-12-0171141115010.1200/GO.21.00097Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni SyndromeRenata Lazari Sandoval0Cibele Masotti1Mariana Petaccia de Macedo2Maurício Fernando Silva Almeida Ribeiro3Ana Carolina Rathsam Leite4Sibele Inacio Meireles5Rodrigo Medeiros Bovolin6Fernando Costa Santini7Rodrigo Ramella Munhoz8Denis Leonardo Fontes Jardim9Artur Katz10Anamaria Aranha Camargo11Gustavo dos Santos Fernandes12Maria Isabel Achatz13Department of Oncology, Hospital Sírio-Libanês, Distrito Federal, BrazilDepartment of Molecular Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Pathology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, Distrito Federal, BrazilDepartment of Pathology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, Distrito Federal, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Molecular Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, Distrito Federal, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilPURPOSELi-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer.MATERIALS AND METHODSWe determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil.RESULTSThe TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria.CONCLUSIONThe identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.https://ascopubs.org/doi/10.1200/GO.21.00097 |
| spellingShingle | Renata Lazari Sandoval Cibele Masotti Mariana Petaccia de Macedo Maurício Fernando Silva Almeida Ribeiro Ana Carolina Rathsam Leite Sibele Inacio Meireles Rodrigo Medeiros Bovolin Fernando Costa Santini Rodrigo Ramella Munhoz Denis Leonardo Fontes Jardim Artur Katz Anamaria Aranha Camargo Gustavo dos Santos Fernandes Maria Isabel Achatz Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome JCO Global Oncology |
| title | Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome |
| title_full | Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome |
| title_fullStr | Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome |
| title_full_unstemmed | Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome |
| title_short | Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome |
| title_sort | identification of the tp53 p r337h variant in tumor genomic profiling should prompt consideration of germline testing for li fraumeni syndrome |
| url | https://ascopubs.org/doi/10.1200/GO.21.00097 |
| work_keys_str_mv | AT renatalazarisandoval identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT cibelemasotti identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT marianapetacciademacedo identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT mauriciofernandosilvaalmeidaribeiro identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT anacarolinarathsamleite identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT sibeleinaciomeireles identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT rodrigomedeirosbovolin identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT fernandocostasantini identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT rodrigoramellamunhoz identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT denisleonardofontesjardim identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT arturkatz identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT anamariaaranhacamargo identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT gustavodossantosfernandes identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome AT mariaisabelachatz identificationofthetp53pr337hvariantintumorgenomicprofilingshouldpromptconsiderationofgermlinetestingforlifraumenisyndrome |