Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica
Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole tr...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Liu, Zhu [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
Gastric linitis plastica (GLP) |
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| Anmerkung: |
© The Author(s) 2022 |
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| Übergeordnetes Werk: |
Enthalten in: Gastric Cancer - Springer-Verlag, 2002, 26(2022), 2 vom: 30. Nov., Seite 203-219 |
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| Übergeordnetes Werk: |
volume:26 ; year:2022 ; number:2 ; day:30 ; month:11 ; pages:203-219 |
| Links: |
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| DOI / URN: |
10.1007/s10120-022-01353-2 |
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SPR049446061 |
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| 520 | |a Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. | ||
| 650 | 4 | |a Gastric cancer (GC) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Gastric linitis plastica (GLP) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Scirrhous gastric cancer (SGC) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Whole exome sequencing (WES) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Whole transcriptome sequencing (WTS) |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Hong, Lian-Lian |4 aut | |
| 700 | 1 | |a Zheng, Jin-Sen |4 aut | |
| 700 | 1 | |a Ling, Zhe-Nan |4 aut | |
| 700 | 1 | |a Zhang, Zhi-Long |4 aut | |
| 700 | 1 | |a Qi, Ya-Nan |4 aut | |
| 700 | 1 | |a Zhang, Xin-Yu |4 aut | |
| 700 | 1 | |a Zhu, Tian-Yu |4 aut | |
| 700 | 1 | |a Wang, Jiu-Li |4 aut | |
| 700 | 1 | |a Han, Jing |4 aut | |
| 700 | 1 | |a Chen, Xiang-Liu |4 aut | |
| 700 | 1 | |a Yu, Qi-Ming |4 aut | |
| 700 | 1 | |a Wang, Shi |4 aut | |
| 700 | 1 | |a Li, Pei |4 aut | |
| 700 | 1 | |a Ling, Zhi-Qiang |0 (orcid)0000-0003-2155-1111 |4 aut | |
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10.1007/s10120-022-01353-2 doi (DE-627)SPR049446061 (SPR)s10120-022-01353-2-e DE-627 ger DE-627 rakwb eng Liu, Zhu verfasserin aut Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 Hong, Lian-Lian aut Zheng, Jin-Sen aut Ling, Zhe-Nan aut Zhang, Zhi-Long aut Qi, Ya-Nan aut Zhang, Xin-Yu aut Zhu, Tian-Yu aut Wang, Jiu-Li aut Han, Jing aut Chen, Xiang-Liu aut Yu, Qi-Ming aut Wang, Shi aut Li, Pei aut Ling, Zhi-Qiang (orcid)0000-0003-2155-1111 aut Enthalten in Gastric Cancer Springer-Verlag, 2002 26(2022), 2 vom: 30. Nov., Seite 203-219 (DE-627)SPR009286586 nnns volume:26 year:2022 number:2 day:30 month:11 pages:203-219 https://dx.doi.org/10.1007/s10120-022-01353-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 26 2022 2 30 11 203-219 |
| spelling |
10.1007/s10120-022-01353-2 doi (DE-627)SPR049446061 (SPR)s10120-022-01353-2-e DE-627 ger DE-627 rakwb eng Liu, Zhu verfasserin aut Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 Hong, Lian-Lian aut Zheng, Jin-Sen aut Ling, Zhe-Nan aut Zhang, Zhi-Long aut Qi, Ya-Nan aut Zhang, Xin-Yu aut Zhu, Tian-Yu aut Wang, Jiu-Li aut Han, Jing aut Chen, Xiang-Liu aut Yu, Qi-Ming aut Wang, Shi aut Li, Pei aut Ling, Zhi-Qiang (orcid)0000-0003-2155-1111 aut Enthalten in Gastric Cancer Springer-Verlag, 2002 26(2022), 2 vom: 30. Nov., Seite 203-219 (DE-627)SPR009286586 nnns volume:26 year:2022 number:2 day:30 month:11 pages:203-219 https://dx.doi.org/10.1007/s10120-022-01353-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 26 2022 2 30 11 203-219 |
| allfields_unstemmed |
10.1007/s10120-022-01353-2 doi (DE-627)SPR049446061 (SPR)s10120-022-01353-2-e DE-627 ger DE-627 rakwb eng Liu, Zhu verfasserin aut Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 Hong, Lian-Lian aut Zheng, Jin-Sen aut Ling, Zhe-Nan aut Zhang, Zhi-Long aut Qi, Ya-Nan aut Zhang, Xin-Yu aut Zhu, Tian-Yu aut Wang, Jiu-Li aut Han, Jing aut Chen, Xiang-Liu aut Yu, Qi-Ming aut Wang, Shi aut Li, Pei aut Ling, Zhi-Qiang (orcid)0000-0003-2155-1111 aut Enthalten in Gastric Cancer Springer-Verlag, 2002 26(2022), 2 vom: 30. Nov., Seite 203-219 (DE-627)SPR009286586 nnns volume:26 year:2022 number:2 day:30 month:11 pages:203-219 https://dx.doi.org/10.1007/s10120-022-01353-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 26 2022 2 30 11 203-219 |
| allfieldsGer |
10.1007/s10120-022-01353-2 doi (DE-627)SPR049446061 (SPR)s10120-022-01353-2-e DE-627 ger DE-627 rakwb eng Liu, Zhu verfasserin aut Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 Hong, Lian-Lian aut Zheng, Jin-Sen aut Ling, Zhe-Nan aut Zhang, Zhi-Long aut Qi, Ya-Nan aut Zhang, Xin-Yu aut Zhu, Tian-Yu aut Wang, Jiu-Li aut Han, Jing aut Chen, Xiang-Liu aut Yu, Qi-Ming aut Wang, Shi aut Li, Pei aut Ling, Zhi-Qiang (orcid)0000-0003-2155-1111 aut Enthalten in Gastric Cancer Springer-Verlag, 2002 26(2022), 2 vom: 30. Nov., Seite 203-219 (DE-627)SPR009286586 nnns volume:26 year:2022 number:2 day:30 month:11 pages:203-219 https://dx.doi.org/10.1007/s10120-022-01353-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 26 2022 2 30 11 203-219 |
| allfieldsSound |
10.1007/s10120-022-01353-2 doi (DE-627)SPR049446061 (SPR)s10120-022-01353-2-e DE-627 ger DE-627 rakwb eng Liu, Zhu verfasserin aut Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 Hong, Lian-Lian aut Zheng, Jin-Sen aut Ling, Zhe-Nan aut Zhang, Zhi-Long aut Qi, Ya-Nan aut Zhang, Xin-Yu aut Zhu, Tian-Yu aut Wang, Jiu-Li aut Han, Jing aut Chen, Xiang-Liu aut Yu, Qi-Ming aut Wang, Shi aut Li, Pei aut Ling, Zhi-Qiang (orcid)0000-0003-2155-1111 aut Enthalten in Gastric Cancer Springer-Verlag, 2002 26(2022), 2 vom: 30. Nov., Seite 203-219 (DE-627)SPR009286586 nnns volume:26 year:2022 number:2 day:30 month:11 pages:203-219 https://dx.doi.org/10.1007/s10120-022-01353-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 26 2022 2 30 11 203-219 |
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Enthalten in Gastric Cancer 26(2022), 2 vom: 30. Nov., Seite 203-219 volume:26 year:2022 number:2 day:30 month:11 pages:203-219 |
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Enthalten in Gastric Cancer 26(2022), 2 vom: 30. Nov., Seite 203-219 volume:26 year:2022 number:2 day:30 month:11 pages:203-219 |
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Liu, Zhu @@aut@@ Hong, Lian-Lian @@aut@@ Zheng, Jin-Sen @@aut@@ Ling, Zhe-Nan @@aut@@ Zhang, Zhi-Long @@aut@@ Qi, Ya-Nan @@aut@@ Zhang, Xin-Yu @@aut@@ Zhu, Tian-Yu @@aut@@ Wang, Jiu-Li @@aut@@ Han, Jing @@aut@@ Chen, Xiang-Liu @@aut@@ Yu, Qi-Ming @@aut@@ Wang, Shi @@aut@@ Li, Pei @@aut@@ Ling, Zhi-Qiang @@aut@@ |
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Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. 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Liu, Zhu misc Gastric cancer (GC) misc Gastric linitis plastica (GLP) misc Scirrhous gastric cancer (SGC) misc Whole exome sequencing (WES) misc Whole transcriptome sequencing (WTS) Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica |
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Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica Gastric cancer (GC) (dpeaa)DE-He213 Gastric linitis plastica (GLP) (dpeaa)DE-He213 Scirrhous gastric cancer (SGC) (dpeaa)DE-He213 Whole exome sequencing (WES) (dpeaa)DE-He213 Whole transcriptome sequencing (WTS) (dpeaa)DE-He213 |
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Liu, Zhu Hong, Lian-Lian Zheng, Jin-Sen Ling, Zhe-Nan Zhang, Zhi-Long Qi, Ya-Nan Zhang, Xin-Yu Zhu, Tian-Yu Wang, Jiu-Li Han, Jing Chen, Xiang-Liu Yu, Qi-Ming Wang, Shi Li, Pei Ling, Zhi-Qiang |
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comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica |
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Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica |
| abstract |
Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. © The Author(s) 2022 |
| abstractGer |
Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. © The Author(s) 2022 |
| abstract_unstemmed |
Background Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. Methods We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. Results Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. Conclusions We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment. © The Author(s) 2022 |
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Hong, Lian-Lian Zheng, Jin-Sen Ling, Zhe-Nan Zhang, Zhi-Long Qi, Ya-Nan Zhang, Xin-Yu Zhu, Tian-Yu Wang, Jiu-Li Han, Jing Chen, Xiang-Liu Yu, Qi-Ming Wang, Shi Li, Pei Ling, Zhi-Qiang |
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