TITLE:
High Incidence of Null-Type Mutations of the TP53 Gene in Japanese Patients with Head and Neck Squamous Cell Carcinoma
AUTHORS:
Yasuhiro Ebihara, Miwako Iwai, Ken Akashi, Takeshi Ito, Go Omura, Yuki Saito, Masafumi Yoshida, Mizuo Ando, Takahiro Asakage, Tatsuya Yamasoba, Yoshinori Murakami
KEYWORDS:
Head and Neck Squamous Cell Carcinoma, TP53 Mutation, KRAS, EGFR, Molecular Marker
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.7,
June
12,
2014
ABSTRACT: Objective: Molecular targeting therapy
has not been generally established in head and neck squamous cell carcinoma
(HNSCC) except for cetuximab treatment for targeting epidermal growth factor
receptor (EGFR). We analyzed alterations of the TP53, KRAS2, and EGFR genes
in Japanese HNSCC to identify subpopulations of tumors potentially susceptible
or not susceptible to specific therapy based on their genetic alterations.
Materials and Methods: A total of 56 Japanese subjects were included in this
study. Genomic DNA of exons 5 - 9 of the TP53, exons 1 and 2 of the KRAS2,
exons 19 - 22 of the EGFR, and their flanking sequences were
amplified by polymerase chain reaction (PCR) followed by direct sequencing.
Splicing variants of EGFR were examined by reverse
transcription (RT)-PCR. Results: Mutations of the TP53 and KRAS genes
were detected in 25 (45%) and 2 (4%) of 56 HNSCC cases, respectively, while
neither mutation nor splicing variant of EGFR was observed.
The TP53 mutation did not correlate with clinical stages or primary
sites of the tumors. The patterns of nucleotide substitutions specific to HNSCC
were not observed. However, the incidence of null-type mutations of the TP53, which
cannot be detected as abnormal by conventional immunohistochemical (IHC)
studies, was significantly higher (10/25; 40%) than that of HNSCC reported in
other countries. Conclusion: Frequent TP53 mutations, especially
null-type mutations, but infrequent or no alterations of the KRAS and EGFR suggest
that the sequencing analysis of theTP53 mutation rather than IHC
analysis of p53 provides a potentially useful marker to predict the response of
HNSCC to chemotherapy or radiotherapy.