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.