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The 112th American Association for Cancer Research (AACR) Annual Meeting has been held in the form of an online virtual meeting on April 10-15, 2021.
The whole exome sequencing research results of Professor Deng Yanhong’s team from the Sixth Affiliated Hospital of Sun Yat-sen University were selected for this AACR poster presentation.
The research results are as follows: Title: Novel genomic characterization in late stage colorectal cancer (genomic characteristics of patients with advanced colorectal cancer) exhibition board number# : 2523 Session Category: Early Tumor Diagnosis and Treatment Session Title: Tumor Prevention and Control, Diagnosis and Treatment [Background] Immunotherapy has become a hot spot in the treatment of advanced colorectal cancer, but it is only effective for microsatellite unstable (MSI) .
Overall, MSI only accounts for about 15% of all colorectal cancers, and most patients still lack effective therapeutic targets.
Therefore, studying the genomic variation characteristics of patients with advanced colorectal cancer is of great significance for finding potential therapeutic targets and improving the overall survival rate of patients.
[Methods] 112 cases of advanced colorectal cancer specimens were sequenced using the whole exome sequencing method, including 86 specimens of primary tumors and 26 specimens of metastatic tumors such as liver and lung.
Compare the genomic variation characteristics of primary and metastatic tumors, left and right half tumors, microsatellite instability (MSI) and microsatellite stable (MSS) tumors [somatic gene mutation, copy number variation (CNV), embryo Line mutations and mutation characteristics, etc.
].
[Results] Patient characteristics: The average age of the enrolled patients was 48 years old, the proportion of men was higher than that of women, the left colon was more than the right colon, and MSI patients accounted for 13% (11/86).
Among the specimens of metastases, liver metastases accounted for 42% (11/26), and lung metastases accounted for 23% (6/26).
MSI vs MSS: Consistent with previous studies, MSI has a higher tumor mutation burden (TMB) than MSS.
Almost all significantly differently mutated genes have a higher mutation frequency in the MSI group.
However, TP53 has a higher mutation frequency in MSS tumors (73% vs 18%).
The GO pathway annotation found that differentially mutated genes were enriched in WNT signaling pathway, epigenetic regulation, etc.
MSI tumors also have a higher incidence of CNV.
Differential CNV genes include GADD45B, RXRA and ID3.
Among germline mutations, POLE has a significantly higher mutation rate in MSI patients.
The mutation characteristics t-SNE analysis showed that the mutation characteristics between MSI and MSS patients were significantly separated.
MSI tumor mutation characteristics are more similar to SBS1, SBS44 and SBS15 mutation characteristics, while MSS is more compatible with SBS10a and SBS6 mutation characteristics.
Left colon vs.
right colon: In order to exclude the influence of MSI, the following analyses are based on MSS samples.
The results showed that even if the influence of MSI was excluded, the TMB and microsatellite instability levels of right hemi-colorectal cancer were still significantly higher than those of the left hemi-colorectal.
Dozens of differentially mutated genes were found between the two groups.
Except for GOLGA6L2 and TP53, most genes have a higher mutation rate in the right colon, such as TENME4, SYNE1, etc.
As far as CNV is concerned, more significant and higher frequency gene copy number variations were also observed in the right colon, including HOXC13, HIST1H2AC, HIST2H3C, WNT1, HOXC11, and BCL11B.
Primary tumor vs.
metastatic tumor: Differential mutation analysis shows that PABPC3 has a significantly higher mutation rate in primary tumors, while 13 genes such as CDH23 and INPP5D have a higher mutation frequency in metastatic tumors.
Previous studies on genomic mutations of metastatic tumors have focused more on somatic mutations.
Here, we found that there are also significant CNV differences between the two groups. [Conclusion] In summary, this study describes the genomic characteristics of Chinese patients with advanced colorectal cancer.
These gene characteristics will help to further understand the molecular mechanism of the occurrence and development of advanced colorectal cancer, and provide ideas for the precise diagnosis and treatment of advanced colorectal cancer and the development of new drugs.
Expert profile Professor Deng Yanhong, chief physician, oncology doctoral tutor, and post-doctoral co-supervisor Assistant to the Dean of the Sixth Affiliated Hospital of Sun Yat-sen University, director of the Cancer Center, Director of the National Drug Clinical Trial Institute (GCP) Center, Guangdong Province Special Support Program Young Top Talents Guangdong Province Medicine Outstanding Young Talent CFDA National Inspector Chinese Colorectal Cancer Diagnosis and Treatment Standards (National Health Commission) Expert Group Member, Chinese Geriatrics Association Oncology Branch Vice Chairman CSWOG Colorectal Cancer Specialized Committee Vice Chairman, Chinese Anti-Cancer Association Tumor Supporting Treatment & Precision Expert Committee Standing Committee CSCO Colorectal Cancer Professional Committee & Youth Committee Standing Committee & Member Chinese Medical Doctor Association Colorectal Tumor Branch Liver Metastasis Committee Standing Committee Member of Guangdong Provincial Women Physician Association Digestive Tumor Professional Committee Member of Guangdong Provincial Medical Association Oncology Branch Source: Zhongshan Department of Oncology, University Sixth Hospital
The whole exome sequencing research results of Professor Deng Yanhong’s team from the Sixth Affiliated Hospital of Sun Yat-sen University were selected for this AACR poster presentation.
The research results are as follows: Title: Novel genomic characterization in late stage colorectal cancer (genomic characteristics of patients with advanced colorectal cancer) exhibition board number# : 2523 Session Category: Early Tumor Diagnosis and Treatment Session Title: Tumor Prevention and Control, Diagnosis and Treatment [Background] Immunotherapy has become a hot spot in the treatment of advanced colorectal cancer, but it is only effective for microsatellite unstable (MSI) .
Overall, MSI only accounts for about 15% of all colorectal cancers, and most patients still lack effective therapeutic targets.
Therefore, studying the genomic variation characteristics of patients with advanced colorectal cancer is of great significance for finding potential therapeutic targets and improving the overall survival rate of patients.
[Methods] 112 cases of advanced colorectal cancer specimens were sequenced using the whole exome sequencing method, including 86 specimens of primary tumors and 26 specimens of metastatic tumors such as liver and lung.
Compare the genomic variation characteristics of primary and metastatic tumors, left and right half tumors, microsatellite instability (MSI) and microsatellite stable (MSS) tumors [somatic gene mutation, copy number variation (CNV), embryo Line mutations and mutation characteristics, etc.
].
[Results] Patient characteristics: The average age of the enrolled patients was 48 years old, the proportion of men was higher than that of women, the left colon was more than the right colon, and MSI patients accounted for 13% (11/86).
Among the specimens of metastases, liver metastases accounted for 42% (11/26), and lung metastases accounted for 23% (6/26).
MSI vs MSS: Consistent with previous studies, MSI has a higher tumor mutation burden (TMB) than MSS.
Almost all significantly differently mutated genes have a higher mutation frequency in the MSI group.
However, TP53 has a higher mutation frequency in MSS tumors (73% vs 18%).
The GO pathway annotation found that differentially mutated genes were enriched in WNT signaling pathway, epigenetic regulation, etc.
MSI tumors also have a higher incidence of CNV.
Differential CNV genes include GADD45B, RXRA and ID3.
Among germline mutations, POLE has a significantly higher mutation rate in MSI patients.
The mutation characteristics t-SNE analysis showed that the mutation characteristics between MSI and MSS patients were significantly separated.
MSI tumor mutation characteristics are more similar to SBS1, SBS44 and SBS15 mutation characteristics, while MSS is more compatible with SBS10a and SBS6 mutation characteristics.
Left colon vs.
right colon: In order to exclude the influence of MSI, the following analyses are based on MSS samples.
The results showed that even if the influence of MSI was excluded, the TMB and microsatellite instability levels of right hemi-colorectal cancer were still significantly higher than those of the left hemi-colorectal.
Dozens of differentially mutated genes were found between the two groups.
Except for GOLGA6L2 and TP53, most genes have a higher mutation rate in the right colon, such as TENME4, SYNE1, etc.
As far as CNV is concerned, more significant and higher frequency gene copy number variations were also observed in the right colon, including HOXC13, HIST1H2AC, HIST2H3C, WNT1, HOXC11, and BCL11B.
Primary tumor vs.
metastatic tumor: Differential mutation analysis shows that PABPC3 has a significantly higher mutation rate in primary tumors, while 13 genes such as CDH23 and INPP5D have a higher mutation frequency in metastatic tumors.
Previous studies on genomic mutations of metastatic tumors have focused more on somatic mutations.
Here, we found that there are also significant CNV differences between the two groups. [Conclusion] In summary, this study describes the genomic characteristics of Chinese patients with advanced colorectal cancer.
These gene characteristics will help to further understand the molecular mechanism of the occurrence and development of advanced colorectal cancer, and provide ideas for the precise diagnosis and treatment of advanced colorectal cancer and the development of new drugs.
Expert profile Professor Deng Yanhong, chief physician, oncology doctoral tutor, and post-doctoral co-supervisor Assistant to the Dean of the Sixth Affiliated Hospital of Sun Yat-sen University, director of the Cancer Center, Director of the National Drug Clinical Trial Institute (GCP) Center, Guangdong Province Special Support Program Young Top Talents Guangdong Province Medicine Outstanding Young Talent CFDA National Inspector Chinese Colorectal Cancer Diagnosis and Treatment Standards (National Health Commission) Expert Group Member, Chinese Geriatrics Association Oncology Branch Vice Chairman CSWOG Colorectal Cancer Specialized Committee Vice Chairman, Chinese Anti-Cancer Association Tumor Supporting Treatment & Precision Expert Committee Standing Committee CSCO Colorectal Cancer Professional Committee & Youth Committee Standing Committee & Member Chinese Medical Doctor Association Colorectal Tumor Branch Liver Metastasis Committee Standing Committee Member of Guangdong Provincial Women Physician Association Digestive Tumor Professional Committee Member of Guangdong Provincial Medical Association Oncology Branch Source: Zhongshan Department of Oncology, University Sixth Hospital
