Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report
Abstract Background Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome characterized by a high familial incidence of various malignancies. It results from pathogenic/likely pathogenic heterozygous constitutional variants of the TP53 gene. Due to impaired DNA damage rep...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-01-01
|
| Series: | Journal of Cancer Research and Clinical Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00432-024-06077-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823863310660927488 |
|---|---|
| author | Carolin Seeling Sonja Dahlum Ralf Marienfeld Vera Jan Brigitte Rack Uwe Gerstenmaier Ambros J. Beer Regine Mayer-Steinacker Wolfgang Thaiss Thomas F. E. Barth Thomas Seufferlein Nadine T. Gaisa Stephan Stilgenbauer Wolfgang Janni Reiner Siebert Hartmut Döhner Verena I. Gaidzik |
| author_facet | Carolin Seeling Sonja Dahlum Ralf Marienfeld Vera Jan Brigitte Rack Uwe Gerstenmaier Ambros J. Beer Regine Mayer-Steinacker Wolfgang Thaiss Thomas F. E. Barth Thomas Seufferlein Nadine T. Gaisa Stephan Stilgenbauer Wolfgang Janni Reiner Siebert Hartmut Döhner Verena I. Gaidzik |
| author_sort | Carolin Seeling |
| collection | DOAJ |
| description | Abstract Background Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome characterized by a high familial incidence of various malignancies. It results from pathogenic/likely pathogenic heterozygous constitutional variants of the TP53 gene. Due to impaired DNA damage repair, conventional cytotoxic therapies or radiotherapy should be avoided whenever feasible to mitigate the high incidence of treatment-related secondary malignancies in these patients. However, there is limited evidence supporting the effectiveness of targeted therapy approaches in LFS patients. Case presentation We present the case of a woman with breast cancer and subsequent osteosarcoma, both treated with surgery and chemotherapy. Constitutional genetic germline testing identified a pathogenic TP53 variant in line with the clinical features of Li-Fraumeni syndrome. Subsequent molecular analysis of the osteosarcoma tissue revealed homozygous loss of the CDKN2A gene locus, warranting treatment with CDK4/6 inhibitor palbociclib. Palbociclib therapy was discontinued after one year with no evidence of disease. One year later, ovarian cancer was diagnosed, with molecular analysis indicating interstitial heterozygous loss of the BRCA2 gene locus, providing a rationale for targeted therapy with the PARP inhibitor olaparib. Conclusions In the era of accessible and comprehensive genetic and phenotypic tumor profiling, this case study of a patient with Li-Fraumeni syndrome underscores the success of precision oncology in harnessing additional somatic oncogenic driver alterations. Furthermore, it emphasizes the indispensable role of an interdisciplinary molecular tumor board, enhancing the awareness of molecular profiling and targeted therapies in patients with rare cancer susceptibility disorders. |
| format | Article |
| id | doaj-art-db6bdf601f6042f699d37e22a6e012a9 |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-db6bdf601f6042f699d37e22a6e012a92025-02-09T12:10:25ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-01-01151111210.1007/s00432-024-06077-7Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case reportCarolin Seeling0Sonja Dahlum1Ralf Marienfeld2Vera Jan3Brigitte Rack4Uwe Gerstenmaier5Ambros J. Beer6Regine Mayer-Steinacker7Wolfgang Thaiss8Thomas F. E. Barth9Thomas Seufferlein10Nadine T. Gaisa11Stephan Stilgenbauer12Wolfgang Janni13Reiner Siebert14Hartmut Döhner15Verena I. Gaidzik16Department of Internal Medicine III, University Hospital UlmInstitute of Human Genetics, University Hospital Ulm and University of UlmInstitute of Pathology, University Hospital UlmInstitute of Human Genetics, University Hospital Ulm and University of UlmDepartment of Gynecology and Obstetrics, University Hospital UlmInstitute of Pathology, University Hospital UlmDepartment of Nuclear Medicine, University Hospital UlmDepartment of Internal Medicine III, University Hospital UlmDepartment of Nuclear Medicine, University Hospital UlmInstitute of Pathology, University Hospital UlmDepartment of Internal Medicine I, University Hospital UlmInstitute of Pathology, University Hospital UlmDepartment of Internal Medicine III, University Hospital UlmDepartment of Gynecology and Obstetrics, University Hospital UlmInstitute of Human Genetics, University Hospital Ulm and University of UlmDepartment of Internal Medicine III, University Hospital UlmDepartment of Internal Medicine III, University Hospital UlmAbstract Background Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome characterized by a high familial incidence of various malignancies. It results from pathogenic/likely pathogenic heterozygous constitutional variants of the TP53 gene. Due to impaired DNA damage repair, conventional cytotoxic therapies or radiotherapy should be avoided whenever feasible to mitigate the high incidence of treatment-related secondary malignancies in these patients. However, there is limited evidence supporting the effectiveness of targeted therapy approaches in LFS patients. Case presentation We present the case of a woman with breast cancer and subsequent osteosarcoma, both treated with surgery and chemotherapy. Constitutional genetic germline testing identified a pathogenic TP53 variant in line with the clinical features of Li-Fraumeni syndrome. Subsequent molecular analysis of the osteosarcoma tissue revealed homozygous loss of the CDKN2A gene locus, warranting treatment with CDK4/6 inhibitor palbociclib. Palbociclib therapy was discontinued after one year with no evidence of disease. One year later, ovarian cancer was diagnosed, with molecular analysis indicating interstitial heterozygous loss of the BRCA2 gene locus, providing a rationale for targeted therapy with the PARP inhibitor olaparib. Conclusions In the era of accessible and comprehensive genetic and phenotypic tumor profiling, this case study of a patient with Li-Fraumeni syndrome underscores the success of precision oncology in harnessing additional somatic oncogenic driver alterations. Furthermore, it emphasizes the indispensable role of an interdisciplinary molecular tumor board, enhancing the awareness of molecular profiling and targeted therapies in patients with rare cancer susceptibility disorders.https://doi.org/10.1007/s00432-024-06077-7Molecular tumor board - Li-Fraumeni syndromePrecision oncologyTargeted therapyCase report |
| spellingShingle | Carolin Seeling Sonja Dahlum Ralf Marienfeld Vera Jan Brigitte Rack Uwe Gerstenmaier Ambros J. Beer Regine Mayer-Steinacker Wolfgang Thaiss Thomas F. E. Barth Thomas Seufferlein Nadine T. Gaisa Stephan Stilgenbauer Wolfgang Janni Reiner Siebert Hartmut Döhner Verena I. Gaidzik Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report Journal of Cancer Research and Clinical Oncology Molecular tumor board - Li-Fraumeni syndrome Precision oncology Targeted therapy Case report |
| title | Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report |
| title_full | Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report |
| title_fullStr | Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report |
| title_full_unstemmed | Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report |
| title_short | Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report |
| title_sort | exploiting somatic oncogenic driver alterations in a patient with li fraumeni syndrome paving the path towards precision medicine a case report |
| topic | Molecular tumor board - Li-Fraumeni syndrome Precision oncology Targeted therapy Case report |
| url | https://doi.org/10.1007/s00432-024-06077-7 |
| work_keys_str_mv | AT carolinseeling exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT sonjadahlum exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT ralfmarienfeld exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT verajan exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT brigitterack exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT uwegerstenmaier exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT ambrosjbeer exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT reginemayersteinacker exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT wolfgangthaiss exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT thomasfebarth exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT thomasseufferlein exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT nadinetgaisa exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT stephanstilgenbauer exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT wolfgangjanni exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT reinersiebert exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT hartmutdohner exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport AT verenaigaidzik exploitingsomaticoncogenicdriveralterationsinapatientwithlifraumenisyndromepavingthepathtowardsprecisionmedicineacasereport |