Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy
<p>Abstract</p> <p>Background</p> <p>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 ide...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-12-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/420 |
| _version_ | 1811263675553546240 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Tsuchiya Eiju |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>and clinical investigations reported that CRC patients with wild-type p53 gene (<it>TP53)</it>-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated <it>TP53</it>-tumors do not. However, these studies evaluated the mutation-status of <it>TP53 </it>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.</p> <p>Methods</p> <p>To evaluate the significance of the <it>TP53 </it>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 <it>TP53 </it>by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR).</p> <p>Results</p> <p>The <it>TP53 </it>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 <it>TP53 </it>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 <it>TP53</it>-R72 showed significantly longer survival times than those with the mutated <it>TP53</it>-P72 when evaluated by overall survival (<it>p = 0.012</it>).</p> <p>Conclusion</p> <p>Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the <it>TP53 </it>mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with tumors carrying <it>TP53 </it>mutation, especially the P72 allele, benefited from 5-FU based postoperative chemotherapy.</p> |
| first_indexed | 2024-04-12T19:49:33Z |
| format | Article |
| id | doaj.art-2f91d43d20ef4c69ae62736980a8f4f1 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T19:49:33Z |
| publishDate | 2009-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-2f91d43d20ef4c69ae62736980a8f4f12022-12-22T03:18:51ZengBMCBMC Cancer1471-24072009-12-019142010.1186/1471-2407-9-420Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapyTsuchiya EijuSakuma YujiMatsukuma ShoichiYoshihara MitsuyoSekiyama AkikoSekiguchi HironobuShiozawa ManabuTsuchida KazuhitoSugano NobuhiroSuda TetsujiGodai Ten-iKameda YoichiAkaike MakotoMiyagi Yohei<p>Abstract</p> <p>Background</p> <p>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 <it>in vitro </it>and clinical investigations reported that CRC patients with wild-type p53 gene (<it>TP53)</it>-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated <it>TP53</it>-tumors do not. However, these studies evaluated the mutation-status of <it>TP53 </it>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.</p> <p>Methods</p> <p>To evaluate the significance of the <it>TP53 </it>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 <it>TP53 </it>by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR).</p> <p>Results</p> <p>The <it>TP53 </it>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 <it>TP53 </it>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 <it>TP53</it>-R72 showed significantly longer survival times than those with the mutated <it>TP53</it>-P72 when evaluated by overall survival (<it>p = 0.012</it>).</p> <p>Conclusion</p> <p>Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the <it>TP53 </it>mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with tumors carrying <it>TP53 </it>mutation, especially the P72 allele, benefited from 5-FU based postoperative chemotherapy.</p>http://www.biomedcentral.com/1471-2407/9/420 |
| spellingShingle | 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 Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy BMC Cancer |
| title | Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy |
| title_full | Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy |
| title_fullStr | Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy |
| title_full_unstemmed | Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy |
| title_short | Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy |
| title_sort | identification of colorectal cancer patients with tumors carrying the it tp53 it mutation on the codon 72 proline allele that benefited most from 5 fluorouracil 5 fu based postoperative chemotherapy |
| url | http://www.biomedcentral.com/1471-2407/9/420 |
| work_keys_str_mv | AT tsuchiyaeiju identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT sakumayuji identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT matsukumashoichi identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT yoshiharamitsuyo identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT sekiyamaakiko identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT sekiguchihironobu identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT shiozawamanabu identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT tsuchidakazuhito identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT suganonobuhiro identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT sudatetsuji identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT godaiteni identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT kamedayoichi identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT akaikemakoto identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy AT miyagiyohei identificationofcolorectalcancerpatientswithtumorscarryingtheittp53itmutationonthecodon72prolineallelethatbenefitedmostfrom5fluorouracil5fubasedpostoperativechemotherapy |