Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in a glioblastoma patient with secondary osteosarcoma: case report and genetic characterization

• Published in: BMC neurology 2022-10, Vol.22 (1), p.1-390, Article 390
• Main Authors: Yi, Guo-zhong, Zhu, Tai-chen, Que, Tian-shi, Li, Zhi-yong, Huang, Guang-long
• Format: Article
• Language: English
• Subjects: Biopsy; Bone cancer; Brain cancer; Cancer therapies; Case Report; Case reports; Chemotherapy; Clinical trials; Combination therapy; Corpus callosum; Development and progression; DNA repair; Dosage and administration; Drug therapy; Drug therapy, Combination; E-cadherin; Femur; Genes; Genetic aspects; Glioblastoma; Glioblastoma multiforme; Mutation; Neoantigens; Neoplasia; Nervous system; O6-methylguanine-DNA methyltransferase; Osteosarcoma; Patients; Pembrolizumab; PTEN protein; Radiation therapy; Remission (Medicine); Sarcoma; Second malignant neoplasm; Temozolomide; Testing; Tumors; Ventricle; Whole-exome sequencing
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-022-02920-x

Background The incidence of osteosarcoma as a secondary neoplasm in glioblastoma patient is extremely rare. The genetic characteristic still remains unclear until now. Case description We reported a 47-year-old female patient with multiple intracranial disseminations and infiltrations (splenium of the corpus callosum and lateral ventricular wall) of a rapid progressive glioblastoma underwent occipital craniotomy and total resection of all the enhancing lesions. Whole-exome sequencing and pathological examination revealed glioblastoma, IDH1 wild type, PTEN deficient, TERT mutated, NF1mutated, MGMT unmethylated. After surgery, the patient received combined therapeutic regimen of TTFields (tumor-treating fields) plus pembrolizumab plus temozolomide and TTFields plus everolimus, which displayed significant clinical benefits. During the combined therapeutic course, an extremely rare secondary malignant neoplasm occurred, femur MR and pathological detection of biopsy tissue demonstrated osteosarcoma. The result of whole-exome sequencing revealed 7 germline mutated genes (EPAS1, SETD2, MSH3, BMPR1A, ERCC4, CDH1, AR). Bioinformatic analysis showed the two germline mutations (MSH3 and ERCC4) induced deficiency in the DNA repair machinery, which resulting in the accumulation of mutations and may generate neoantigens contributing to the development of a secondary osteosarcoma in this case. Conclusion Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in this case. Germline MSH3 and ERCC4 mutation may induce a secondary osteosarcoma in glioblastoma patients. Keywords: Second malignant neoplasm, Osteosarcoma, Glioblastoma, Whole-exome sequencing, Combination therapy