title: The influence of TP53 mutations on the prognosis of patients with early stage non-small cell lung cancer may depend on the intratumor heterogeneity of the mutations.
abstract: A large number of studies have evaluated the impact of TP53 mutations on the prognosis of patients with non-small cell lung cancer (NSCLC); however, the results of these studies are still controversial. Recently, considerable intratumor heterogeneity for genetic alterations has been demonstrated in various human cancers, including lung cancer. In the present study, we evaluated TP53 mutations in NSCLCs by direct sequencing and observed remarkable variation in the values of relative intensity (RI, the height of the peak of mutated allele/the height of the peak of non-mutated allele) of the mutations. We also examined whether the RI values were associated with intratumor heterogeneity of TP53 mutations. In addition, we evaluated the relationship between TP53 mutations and survival outcome. The patients with a TP53 mutation did not have significantly worse survival compared to those without the mutation. However, when tumors with a TP53 mutation were categorized into two groups, those with a low and those with a high RI, the latter group had significantly worse survival compared to those with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21-5.48, P = 0.01), whereas the former group did not. These results suggest that intratumor genetic heterogeneity may be an important factor in determining the role of TP53 mutations on the prognosis of NSCLC patients.
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Yup
authors.initials: Y
authors.lastname: Hwangbo
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Shin
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TP53 mutation; intratumor heterogeneity; non-small cell lung cancer; prognosis; relative intensity