Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy
This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10353 |
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| author | You-Kang Chang Hui-Hwa Tseng Chung-Man Leung Kuo-Cheng Lu Kuo-Wang Tsai |
| author_facet | You-Kang Chang Hui-Hwa Tseng Chung-Man Leung Kuo-Cheng Lu Kuo-Wang Tsai |
| author_sort | You-Kang Chang |
| collection | DOAJ |
| description | This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous <i>p53</i>, <i>APC</i>, <i>KRAS</i>, <i>CDKN2A</i>, and <i>EGFR</i> mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. <i>BRAF</i>, <i>FBXW7</i>, <i>PTEN</i>, and <i>SMAD4</i> mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: <i>ATM</i>, <i>BRAF</i>, <i>CDKN2A</i>, <i>EGFR</i>, <i>FLT3</i>, <i>GNA11</i>, <i>KDR</i>, <i>KIT</i>, <i>PIK3CA</i>, <i>PTEN</i>, <i>PTPN11</i>, <i>SMAD4</i>, and <i>TP53</i>. In addition, <i>APC</i>, <i>BRAF</i>, <i>FBXW7</i>, <i>KRAS</i>, <i>SMAD4</i>, and <i>TP53</i> mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of <i>BRAF</i>, <i>SMAD4</i>, and <i>TP53</i> genetic variants in the outcomes of patients with nCRT. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:26Z |
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| spelling | doaj.art-1dfd15e68a1e49ab8787fcb02d5c20f22023-11-23T16:40:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181035310.3390/ijms231810353Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant ChemoradiotherapyYou-Kang Chang0Hui-Hwa Tseng1Chung-Man Leung2Kuo-Cheng Lu3Kuo-Wang Tsai4Department of Radiation Oncology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, TaiwanDepartment of Anatomic Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 97004, TaiwanDepartment of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung 81341, TaiwanDivision of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 97004, TaiwanDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, TaiwanThis study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous <i>p53</i>, <i>APC</i>, <i>KRAS</i>, <i>CDKN2A</i>, and <i>EGFR</i> mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. <i>BRAF</i>, <i>FBXW7</i>, <i>PTEN</i>, and <i>SMAD4</i> mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: <i>ATM</i>, <i>BRAF</i>, <i>CDKN2A</i>, <i>EGFR</i>, <i>FLT3</i>, <i>GNA11</i>, <i>KDR</i>, <i>KIT</i>, <i>PIK3CA</i>, <i>PTEN</i>, <i>PTPN11</i>, <i>SMAD4</i>, and <i>TP53</i>. In addition, <i>APC</i>, <i>BRAF</i>, <i>FBXW7</i>, <i>KRAS</i>, <i>SMAD4</i>, and <i>TP53</i> mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of <i>BRAF</i>, <i>SMAD4</i>, and <i>TP53</i> genetic variants in the outcomes of patients with nCRT.https://www.mdpi.com/1422-0067/23/18/10353rectal carcinomacancer panelnext-generation sequencingchemoradiotherapy |
| spellingShingle | You-Kang Chang Hui-Hwa Tseng Chung-Man Leung Kuo-Cheng Lu Kuo-Wang Tsai Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy International Journal of Molecular Sciences rectal carcinoma cancer panel next-generation sequencing chemoradiotherapy |
| title | Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy |
| title_full | Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy |
| title_fullStr | Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy |
| title_full_unstemmed | Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy |
| title_short | Targeted Next-Generation Sequencing-Based Multiple Gene Mutation Profiling of Patients with Rectal Adenocarcinoma Receiving or Not Receiving Neoadjuvant Chemoradiotherapy |
| title_sort | targeted next generation sequencing based multiple gene mutation profiling of patients with rectal adenocarcinoma receiving or not receiving neoadjuvant chemoradiotherapy |
| topic | rectal carcinoma cancer panel next-generation sequencing chemoradiotherapy |
| url | https://www.mdpi.com/1422-0067/23/18/10353 |
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