Cargando…
Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
Large‐scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394152/ https://www.ncbi.nlm.nih.gov/pubmed/37189003 http://dx.doi.org/10.1111/cas.15834 |
_version_ | 1785083304643395584 |
---|---|
author | Shida, Dai Kuchiba, Aya Shibata, Tatsuhiro Hamaguchi, Tetsuya Yamasaki, Satoshi Ito, Masaaki Kobatake, Takaya Tonooka, Toru Masaki, Tadahiko Shiozawa, Manabu Takii, Yasumasa Uetake, Hiroyuki Okamura, Shu Ojima, Hitoshi Kazama, Shinsuke Takeyama, Hiroshi Kanato, Keisuke Shimada, Yasuhiro Murakami, Yoshinori Kanemitsu, Yukihide |
author_facet | Shida, Dai Kuchiba, Aya Shibata, Tatsuhiro Hamaguchi, Tetsuya Yamasaki, Satoshi Ito, Masaaki Kobatake, Takaya Tonooka, Toru Masaki, Tadahiko Shiozawa, Manabu Takii, Yasumasa Uetake, Hiroyuki Okamura, Shu Ojima, Hitoshi Kazama, Shinsuke Takeyama, Hiroshi Kanato, Keisuke Shimada, Yasuhiro Murakami, Yoshinori Kanemitsu, Yukihide |
author_sort | Shida, Dai |
collection | PubMed |
description | Large‐scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted‐capture sequencing of 171 potentially colorectal cancer‐associated genes was performed, and somatic single‐nucleotide variants and insertion–deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra‐mutated tumors with POLE mutations. Genes with alterations associated with relapse‐free survival were analyzed using multivariable Cox regression models. In all patients (184 right‐sided, 350 left‐sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty‐one tumors were hypermutated (5.8%; 14.1% right‐sided, 1.4% left‐sided). Modest associations were observed: poorer relapse‐free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse‐free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse‐free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse‐free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer. |
format | Online Article Text |
id | pubmed-10394152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103941522023-08-03 Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910 Shida, Dai Kuchiba, Aya Shibata, Tatsuhiro Hamaguchi, Tetsuya Yamasaki, Satoshi Ito, Masaaki Kobatake, Takaya Tonooka, Toru Masaki, Tadahiko Shiozawa, Manabu Takii, Yasumasa Uetake, Hiroyuki Okamura, Shu Ojima, Hitoshi Kazama, Shinsuke Takeyama, Hiroshi Kanato, Keisuke Shimada, Yasuhiro Murakami, Yoshinori Kanemitsu, Yukihide Cancer Sci ORIGINAL ARTICLES Large‐scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted‐capture sequencing of 171 potentially colorectal cancer‐associated genes was performed, and somatic single‐nucleotide variants and insertion–deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra‐mutated tumors with POLE mutations. Genes with alterations associated with relapse‐free survival were analyzed using multivariable Cox regression models. In all patients (184 right‐sided, 350 left‐sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty‐one tumors were hypermutated (5.8%; 14.1% right‐sided, 1.4% left‐sided). Modest associations were observed: poorer relapse‐free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse‐free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse‐free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse‐free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer. John Wiley and Sons Inc. 2023-05-15 /pmc/articles/PMC10394152/ /pubmed/37189003 http://dx.doi.org/10.1111/cas.15834 Text en © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Shida, Dai Kuchiba, Aya Shibata, Tatsuhiro Hamaguchi, Tetsuya Yamasaki, Satoshi Ito, Masaaki Kobatake, Takaya Tonooka, Toru Masaki, Tadahiko Shiozawa, Manabu Takii, Yasumasa Uetake, Hiroyuki Okamura, Shu Ojima, Hitoshi Kazama, Shinsuke Takeyama, Hiroshi Kanato, Keisuke Shimada, Yasuhiro Murakami, Yoshinori Kanemitsu, Yukihide Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910 |
title | Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
|
title_full | Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
|
title_fullStr | Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
|
title_full_unstemmed | Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
|
title_short | Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910
|
title_sort | genomic landscape and its prognostic significance in stage iii colorectal cancer: jcog1506a1, an ancillary of jcog0910 |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394152/ https://www.ncbi.nlm.nih.gov/pubmed/37189003 http://dx.doi.org/10.1111/cas.15834 |
work_keys_str_mv | AT shidadai genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT kuchibaaya genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT shibatatatsuhiro genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT hamaguchitetsuya genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT yamasakisatoshi genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT itomasaaki genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT kobataketakaya genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT tonookatoru genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT masakitadahiko genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT shiozawamanabu genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT takiiyasumasa genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT uetakehiroyuki genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT okamurashu genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT ojimahitoshi genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT kazamashinsuke genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT takeyamahiroshi genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT kanatokeisuke genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT shimadayasuhiro genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT murakamiyoshinori genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 AT kanemitsuyukihide genomiclandscapeanditsprognosticsignificanceinstageiiicolorectalcancerjcog1506a1anancillaryofjcog0910 |