Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,...Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,100 deaths of CRC in China, accounting for 9.87% and 8.01% of all malignancies. The first version of the Chinese Society of Clinical Oncology(CSCO) guidelines was released in April2017, and has been updated annually based on the latest clinical research data and the availability of new drugs(2-4). Here, we present the main updates of the 2021 version compared to 2020 version.展开更多
Objective:In some patients with adenomatous polyposis,an identifiable pathogenic variant of known associated genes cannot be found.Researchers have studied this for decades;however,few new genes have been identified.M...Objective:In some patients with adenomatous polyposis,an identifiable pathogenic variant of known associated genes cannot be found.Researchers have studied this for decades;however,few new genes have been identified.Methods:Adenomatous polyposis coli(APC)negative polyposis patients were identified through next-generation sequencing and multiplex ligation-dependent probe amplification.Then,whole-exome sequencing(WES)was used to determine candidate genes harboring pathogenic variants.Functional experiments were performed to explore their effects.Subsequently,using Sanger sequencing,we found other polyposis patients carrying variants of the DUOX2 gene,encoding dual oxidase 2,and analyzed them.Results:From 88 patients with suspected familial adenomatous polyposis,25 unrelated APC negative polyposis patients were identified.Based on the WES results of 3 patients and 2 healthy relatives from a family,the germline nonsense variant(c.1588 A>T;p.K530 X)of the DUOX2 gene was speculated to play a decisive role in the pedigree in relation to adenomatous polyposis.During functional experiments,we observed that the truncated protein,h Duox2 K530,was overexpressed in the adenoma in a carrier of the DUOX2 nonsense variant,causing abnormal cell proliferation through endoplasmic reticulum(ER)retention.In addition,we found two unrelated APC negative patients carrying DUOX2 missense variants(c.3329 G>A,p.R1110 Q;c.4027 C>T,p.L1343 F).Given the results of the in silico analysis,these two missense variants might exert a negative influence on the function of h Duox2.Conclusions:To our knowledge,this is the first study that reports the possible association of DUOX2 germline variants with adenomatous polyposis.With an autosomal dominant inheritance,it causes ER retention,inducing an unfolded protein response.展开更多
Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of present...Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).展开更多
In the published paper1,the author's organization information on page 215 contained errors.The author information has been updated to correct the errors.The errors do not affect the conclusions of this article.We ...In the published paper1,the author's organization information on page 215 contained errors.The author information has been updated to correct the errors.The errors do not affect the conclusions of this article.We apologize for the errors and for any confusion they may have caused.展开更多
基金supported by the National Key R&D Program of China (No. 2018YFC1312100)the National Natural Science Foundation of China (No. 81872481)Traditional Chinese Medicine (Integrated Chinese and Western Medicine) Key Discipline Construction Project of Zhejiang Province (No. 2017-XK-A40)。
文摘Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,100 deaths of CRC in China, accounting for 9.87% and 8.01% of all malignancies. The first version of the Chinese Society of Clinical Oncology(CSCO) guidelines was released in April2017, and has been updated annually based on the latest clinical research data and the availability of new drugs(2-4). Here, we present the main updates of the 2021 version compared to 2020 version.
基金supported by the National Key R&D Program of China(Grant No.2017YFC0908200)the National Natural Science Foundation of China(Grant Nos.81872481 and 81902956)。
文摘Objective:In some patients with adenomatous polyposis,an identifiable pathogenic variant of known associated genes cannot be found.Researchers have studied this for decades;however,few new genes have been identified.Methods:Adenomatous polyposis coli(APC)negative polyposis patients were identified through next-generation sequencing and multiplex ligation-dependent probe amplification.Then,whole-exome sequencing(WES)was used to determine candidate genes harboring pathogenic variants.Functional experiments were performed to explore their effects.Subsequently,using Sanger sequencing,we found other polyposis patients carrying variants of the DUOX2 gene,encoding dual oxidase 2,and analyzed them.Results:From 88 patients with suspected familial adenomatous polyposis,25 unrelated APC negative polyposis patients were identified.Based on the WES results of 3 patients and 2 healthy relatives from a family,the germline nonsense variant(c.1588 A>T;p.K530 X)of the DUOX2 gene was speculated to play a decisive role in the pedigree in relation to adenomatous polyposis.During functional experiments,we observed that the truncated protein,h Duox2 K530,was overexpressed in the adenoma in a carrier of the DUOX2 nonsense variant,causing abnormal cell proliferation through endoplasmic reticulum(ER)retention.In addition,we found two unrelated APC negative patients carrying DUOX2 missense variants(c.3329 G>A,p.R1110 Q;c.4027 C>T,p.L1343 F).Given the results of the in silico analysis,these two missense variants might exert a negative influence on the function of h Duox2.Conclusions:To our knowledge,this is the first study that reports the possible association of DUOX2 germline variants with adenomatous polyposis.With an autosomal dominant inheritance,it causes ER retention,inducing an unfolded protein response.
基金supported by the Provincial Key R&D Program of Zhejiang Province(Grant No.2021C03125)the Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-tongshu2021/ms-0003).
文摘Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).
文摘In the published paper1,the author's organization information on page 215 contained errors.The author information has been updated to correct the errors.The errors do not affect the conclusions of this article.We apologize for the errors and for any confusion they may have caused.
