{"corpus_id":12935948,"paper_sha":null,"doi":"10.1186/1471-2407-13-200","arxiv_id":null,"pmid":23617638,"pmcid":"3640970","mag_id":2084326118,"dblp_id":null,"acl_id":null,"title":"Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery","year":2013,"publication_date":"2013-04-23","venue":"BMC Cancer","journal":{"name":"BMC Cancer","pages":"200 - 200","volume":"13"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","Review"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Medicine"],"reference_count":40,"citation_count":29,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aged, 80 and over","mj":false,"ui":"D000369"},{"d":"Carcinoma","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"secondary","mj":false,"ui":"Q000556"},{"q":"therapy","mj":true,"ui":"Q000628"}],"ui":"D002277"},{"d":"Chemoradiotherapy, Adjuvant","mj":false,"ui":"D059186"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Kaplan-Meier Estimate","mj":false,"ui":"D053208"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Mutation Rate","mj":false,"ui":"D059645"},{"d":"Neoadjuvant Therapy","mj":false,"ui":"D020360"},{"d":"Neoplasm Metastasis","mj":false,"ui":"D009362"},{"d":"Neoplasm Recurrence, Local","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D009364"},{"d":"Nuclear Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D009687"},{"d":"Proto-Oncogene Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D011518"},{"d":"Proto-Oncogene Proteins B-raf","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D048493"},{"d":"Proto-Oncogene Proteins p21(ras)","mj":false,"ui":"D016283"},{"d":"Rectal Neoplasms","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"},{"q":"therapy","mj":true,"ui":"Q000628"}],"ui":"D012004"},{"d":"Retrospective Studies","mj":false,"ui":"D012189"},{"d":"Transcription Factors","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D014157"},{"d":"ras Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D018631"}],"chemicals":[{"n":"KRAS protein, human","ui":"C117307","reg":"0"},{"n":"Nuclear Proteins","ui":"D009687","reg":"0"},{"n":"PI3KCA protein, human","ui":"C503859","reg":"0"},{"n":"Proto-Oncogene Proteins","ui":"D011518","reg":"0"},{"n":"Transcription Factors","ui":"D014157","reg":"0"},{"n":"BRAF protein, human","ui":"C482119","reg":"EC 2.7.11.1"},{"n":"Proto-Oncogene Proteins B-raf","ui":"D048493","reg":"EC 2.7.11.1"},{"n":"Proto-Oncogene Proteins p21(ras)","ui":"D016283","reg":"EC 3.6.5.2"},{"n":"ras Proteins","ui":"D018631","reg":"EC 3.6.5.2"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://bmccancer.biomedcentral.com/counter/pdf/10.1186/1471-2407-13-200","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/49296f94e378f3e2b094c38323c452ced0ae8cd5","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BackgroundConventional treatment for locally advanced rectal cancer usually combines neoadjuvant radiochemotherapy and surgery. Until recently, there have been limited predictive factors (clinical or biological) for rectal tumor response to conventional treatment. KRAS, BRAF and PIK3CA mutations are commonly found in colon cancers. In this study, we aimed to determine the mutation frequencies of KRAS, BRAF and PIK3CA and to establish whether such mutations may be used as prognostic and/or predictive factors in rectal cancer patients.MethodsWe retrospectively reviewed the clinical and biological data of 98 consecutive operated patients between May 2006 and September 2009. We focused in patients who received surgery in our center after radiochemotherapy and in which tumor samples were available.ResultsIn the 98 patients with a rectal cancer, the median follow-up time was 28.3 months (4–74). Eight out of ninety-eight patients experienced a local recurrence (8%) and 17/98 developed distant metastasis (17%). KRAS, BRAF and PIK3CA were identified respectively in 23 (23.5%), 2 (2%) and 4 (4%) patients. As described in previous studies, mutations in KRAS and BRAF were mutually exclusive. No patient with local recurrence exhibited KRAS or PIK3CA mutation and one harbored BRAF mutation (12.5%). Of the seventeen patients with distant metastasis (17%), 5 were presenting KRAS mutation (29%), one BRAF (5%) and one PIK3CA mutation (5%). No relationship was seen between PIK3CA, KRAS or BRAF mutation and local or distant recurrences.ConclusionThe frequencies of KRAS, BRAF and PIK3CA mutations in our study were lower than the average frequencies reported in colorectal cancers and no significant correlation was found between local/distant recurrences and KRAS, BRAF or PIK3CA mutations. Future studies with greater number of patients, longer follow-up time and greater power to predict associations are necessary to fully understand this relationship.","claims":[{"public_id":"cl_a87f1f26ef1b6ffe6a80899e6817aab7","status":"active","text":"KRAS and BRAF mutations were mutually exclusive in the analyzed rectal cancer samples.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_a87f1f26ef1b6ffe6a80899e6817aab7"},{"public_id":"cl_e7203f4a9f1b0261f9eef1ed32d792dd","status":"active","text":"KRAS, BRAF, and PIK3CA mutations were detected in 23.5%, 2%, and 4% of the 98 rectal cancer patients, respectively.","confidence":0.99,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e7203f4a9f1b0261f9eef1ed32d792dd"},{"public_id":"cl_e1494eb1a08d44d88b37c8a4dd08fd51","status":"active","text":"No significant relationship was found between KRAS, BRAF, or PIK3CA mutation status and local or distant recurrence after neoadjuvant radiochemotherapy and surgery.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e1494eb1a08d44d88b37c8a4dd08fd51"},{"public_id":"cl_5da865a44b41660463be051d70af7307","status":"active","text":"The observed mutation frequencies for KRAS, BRAF, and PIK3CA were lower than the average frequencies reported in colorectal cancers.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5da865a44b41660463be051d70af7307"}],"concepts":[{"public_id":"co_1b25ac77580b3b70546d16464478c54d","status":"active","name":"PIK3CA","description":"A gene encoding a phosphatidylinositol 3-kinase catalytic subunit and assessed here for mutation status.","types":["gene"],"aliases":["PI3KCA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1b25ac77580b3b70546d16464478c54d"},{"public_id":"co_2f7fa4c67ed2cdbf1190fa099ca060f4","status":"active","name":"KRAS","description":"A gene commonly mutated in colorectal tumors and evaluated here as a molecular marker.","types":["gene"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2f7fa4c67ed2cdbf1190fa099ca060f4"},{"public_id":"co_5502ba3d9863144340fd3e95cbe3e2f9","status":"active","name":"neoadjuvant radiochemotherapy","description":"Preoperative treatment combining radiation therapy and chemotherapy.","types":["treatment"],"aliases":["radiochemotherapy"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5502ba3d9863144340fd3e95cbe3e2f9"},{"public_id":"co_64531d3a9abc3067fe451f50be4399ea","status":"active","name":"BRAF","description":"A gene encoding a signaling protein and assessed here for mutation status in rectal cancer.","types":["gene"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_64531d3a9abc3067fe451f50be4399ea"},{"public_id":"co_7e1aeb9a57df6b6f29925c38819cebce","status":"active","name":"surgery","description":"Operative removal of the rectal tumor after preoperative treatment.","types":["treatment"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7e1aeb9a57df6b6f29925c38819cebce"},{"public_id":"co_ae23e49d76d0e06ef3a37455b7002272","status":"active","name":"local recurrence","description":"Return of tumor growth at or near the original rectal tumor site.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ae23e49d76d0e06ef3a37455b7002272"},{"public_id":"co_e1d689ac9f3e040f1f176213ef3840b3","status":"active","name":"rectal cancer samples","description":"Tumor specimens collected from operated rectal cancer patients for mutation analysis.","types":["sample"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e1d689ac9f3e040f1f176213ef3840b3"},{"public_id":"co_e2a563ca731a849e827182f7225e8c53","status":"active","name":"rectal carcinoma","description":"A malignant tumor arising in the rectum.","types":["cancer","condition"],"aliases":["rectal cancer"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_e2a563ca731a849e827182f7225e8c53"},{"public_id":"co_f9afc41cb0b0d25b3a97d26a4bebfd31","status":"active","name":"distant metastasis","description":"Spread of cancer to sites away from the original rectal tumor.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_f9afc41cb0b0d25b3a97d26a4bebfd31"}],"external_ids":{"DOI":"10.1186/1471-2407-13-200","ArXiv":null,"PubMed":23617638,"PubMedCentral":"3640970","MAG":2084326118,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://bmccancer.biomedcentral.com/counter/pdf/10.1186/1471-2407-13-200","landing_url":"https://www.semanticscholar.org/paper/49296f94e378f3e2b094c38323c452ced0ae8cd5","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBY","status":"GOLD","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631909,"paper_uid":"b703d905-b0e6-45da-9962-15b019fe1701","canonical_identity":{"paper_id":631909,"paper_uid":"b703d905-b0e6-45da-9962-15b019fe1701","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/12935948"}