Academic Journal

Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy

التفاصيل البيبلوغرافية
العنوان: Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy
المؤلفون: Tsuchiya Eiju, Sakuma Yuji, Matsukuma Shoichi, Yoshihara Mitsuyo, Sekiyama Akiko, Sekiguchi Hironobu, Shiozawa Manabu, Tsuchida Kazuhito, Sugano Nobuhiro, Suda Tetsuji, Godai Ten-i, Kameda Yoichi, Akaike Makoto, Miyagi Yohei
المصدر: BMC Cancer, Vol 9, Iss 1, p 420 (2009)
بيانات النشر: BMC
سنة النشر: 2009
المجموعة: Directory of Open Access Journals: DOAJ Articles
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Background Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene ( TP53) -tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated TP53 -tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined. Methods To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR). Results The TP53 mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53 -R72 showed significantly longer survival times than those with the mutated TP53 -P72 when evaluated by overall survival ( p = 0.012 ). Conclusion Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 1471-2407
Relation: http://www.biomedcentral.com/1471-2407/9/420; https://doaj.org/toc/1471-2407; https://doaj.org/article/2f91d43d20ef4c69ae62736980a8f4f1
DOI: 10.1186/1471-2407-9-420
الاتاحة: https://doi.org/10.1186/1471-2407-9-420
https://doaj.org/article/2f91d43d20ef4c69ae62736980a8f4f1
رقم الانضمام: edsbas.7805C9BC
قاعدة البيانات: BASE
الوصف
تدمد:14712407
DOI:10.1186/1471-2407-9-420