3 | DISCUSSION
MTT is malignant peripheral nerve sheath tumor (MPNST) with rhabdomyosarcomatous differentiation.4 MPNSTs usually appear in patients with autosomal dominant disease, neurofibromatosis type 1 (NF-1), with sporadic occurrence.5 NF1 gene frameshift mutation was detected in the tumor specimen of the patient, while no evidence of clinical manifestations of NF-1 was found.
The occurrence of MTT is related to missense mutation and loss of heterozygosity of NF1 gene. As a tumor suppressor gene, NF1 gene is located on the long arm of chromosome 17 (17q11.2) and encodes class I neurofibroma protein.6Mutations in NF1 gene can cause abnormal activation of RAS signaling pathways and activate the PI3K/AKT/mTOR signaling pathways. It is suggested that tumors with NF1 mutations are sensitive to inhibitors targeting mTOR and MEK. The protein encoded by NF1 gene of the tumor sample from the patient displayed a frameshift mutation at the 1488th amino acid, with a gene mutation frequency of 90.2%. The NF1-p.Thr1488LysfsTer5 mutation carried by the tumor sample of the patient was a frameshift mutation, which had not been included in Catalogue of Somatic Mutations in Cancer (COSMIC). Frameshift mutations can lead to premature stop codons to encode truncated protein products, which may affect the protein functions.
Neurofibromatosis is associated with an increased risk of many individual cancers, including breast cancer7. FANCD2 gene is breast cancer susceptibility and FANCD2 is a potential risk factor of breast cancer.8Once FANCD2 gene was ubiquitinated, it participates in the transduction and regulation of various biological processes such as DNA damage repair, cell cycle regulation, gene transcription, etc. via the FA/BRCA pathway.9 FANCD2 gene mutation leading to defects in DNA damage repair may be one of the causes of MTT occurrence and recurrence. The 1178th amino acid of FANCD2 gene-encoded protein in the patient changed from serine to cysteine, with a gene mutation frequency of 24.7%. The FANCD2-p.Ser1178Cys mutation carried by the tumor sample of the patient was a missense mutation, which had not been included in COSMIC, and its impact on protein functions is still unknown.
This is the first case reporting the coexistence of FANCD2 and NF1 mutations in MTT, while the relationship between the genetic testing results of MTT and its clinical manifestations is still unclear, which requires further research. It is worth noting that radical surgical resection of MTT, whether combined with chemotherapy and radiotherapy, results in a significantly better prognosis than subtotal resection.10-11 Therefore, as the initial operation, the complete resection has crucial influences on the prognosis and recurrence of MTT, which deserves special attention by clinicians.