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Recently, Zhu Zhenggang, Yu Yingyan, Chen Hongzhuan, Wei Chaochun of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine published a research paper
titled "Pangenomic analysis of Chinese gastric cancer" in Nature Communications.
For the first time, the study uses a new pangenomic approach to human tumor genome research
.
By constructing the pangenome of gastric cancer population, and then comparing the whole genome sequencing data of each case with pangenome as a reference, the existence-deletion of new variants
in the individual genome of gastric cancer is delineated.
And in sequences that do not match the reference genome there is a new set of genes missing from the human reference genome
.
The research results provide an important reference
for the analysis of the molecular genetic background of the high incidence of Chinese gastric cancer.
The Human Reference Genome "Sketch" released in 2001 is a major research result of the International Human Genome Project, which has greatly promoted the study
of disease genome and cancer genome.
Because the DNA samples for the construction of human reference genes are taken from a small number of individual donors, there is insufficient sample selection and it is difficult to fully reflect the genomic diversity
of different regions and ethnic groups.
Pangenome, which refers to the sum of all individual genomes in a population, reflects genetic diversity more than a single human reference genome, and may be more appropriate
to use pangenomics as a reference in human disease-related genomics research.
The gastric cancer research team of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine and the genomics research team of Shanghai Jiao Tong University School of Life Science and Technology, together with multiple research teams such as Fudan University Affiliated Cancer Hospital and Shanghai Institute of Interdisciplinary Sciences of Shanghai University of Traditional Chinese Medicine, have independently constructed a human pan-genome automated analysis process (Genome Biology, 2019) after five years of joint interdisciplinary scientific and technological research.
20:149) and this applied study on gastric cancer genome sequencing samples (Nature Communications, 2022, 13:5412
).
In this study, HUPAN was used to analyze the whole genome depth sequencing data of 185 pairs of gastric cancer and paracancerous tissues (a total of 370 samples), and a gastric cancer pangenome containing the human reference genome (GRCh38) and 80.
88 Mbp new sequences was constructed
.
Among them, the new sequence contains at least 14 new genes
.
Then, the individual genome is compared with the pangenome as a reference to identify a new genetic variant of the stomach cancer disease - the presence-absence variations (PAVs)
of genes.
A total of 261 non-essential genes were found in the gastric cancer population, of which 195 non-essential genes belonged to the paracancerous and cancerous tissue common genes (186 human reference genomic genes and 9 new sequence genes
).
Comparing these genes with genome sequencing datasets of healthy people of different races in public databases found that the presence or absence of some non-essential genes can increase susceptibility
to gastric cancer.
For example, the non-essential genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 were significantly more likely to be lost in gastric cancer populations than in other populations
.
For those new genes predicted by sequences other than the human reference genome, the research team used the long-read long sequences of the three-generation sequencing to conduct chromosomal localization research, and successfully localized the new gene GC0643 to the 9q34.
2 locus
.
The use of cell line model in vitro overexpression of GC0643 gene significantly inhibits tumor cell growth, migration invasion, cell cycle progression and promotes apoptosis, and this tumor suppressor effect can be reversed
by gene retraction.
The new gene GC0643 has been certified by the International NCBI Database (GenBank: MW194843.
1
).
Thesis Links:
titled "Pangenomic analysis of Chinese gastric cancer" in Nature Communications.
For the first time, the study uses a new pangenomic approach to human tumor genome research
.
By constructing the pangenome of gastric cancer population, and then comparing the whole genome sequencing data of each case with pangenome as a reference, the existence-deletion of new variants
in the individual genome of gastric cancer is delineated.
And in sequences that do not match the reference genome there is a new set of genes missing from the human reference genome
.
The research results provide an important reference
for the analysis of the molecular genetic background of the high incidence of Chinese gastric cancer.
The Human Reference Genome "Sketch" released in 2001 is a major research result of the International Human Genome Project, which has greatly promoted the study
of disease genome and cancer genome.
Because the DNA samples for the construction of human reference genes are taken from a small number of individual donors, there is insufficient sample selection and it is difficult to fully reflect the genomic diversity
of different regions and ethnic groups.
Pangenome, which refers to the sum of all individual genomes in a population, reflects genetic diversity more than a single human reference genome, and may be more appropriate
to use pangenomics as a reference in human disease-related genomics research.
The gastric cancer research team of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine and the genomics research team of Shanghai Jiao Tong University School of Life Science and Technology, together with multiple research teams such as Fudan University Affiliated Cancer Hospital and Shanghai Institute of Interdisciplinary Sciences of Shanghai University of Traditional Chinese Medicine, have independently constructed a human pan-genome automated analysis process (Genome Biology, 2019) after five years of joint interdisciplinary scientific and technological research.
20:149) and this applied study on gastric cancer genome sequencing samples (Nature Communications, 2022, 13:5412
).
In this study, HUPAN was used to analyze the whole genome depth sequencing data of 185 pairs of gastric cancer and paracancerous tissues (a total of 370 samples), and a gastric cancer pangenome containing the human reference genome (GRCh38) and 80.
88 Mbp new sequences was constructed
.
Among them, the new sequence contains at least 14 new genes
.
Then, the individual genome is compared with the pangenome as a reference to identify a new genetic variant of the stomach cancer disease - the presence-absence variations (PAVs)
of genes.
A total of 261 non-essential genes were found in the gastric cancer population, of which 195 non-essential genes belonged to the paracancerous and cancerous tissue common genes (186 human reference genomic genes and 9 new sequence genes
).
Comparing these genes with genome sequencing datasets of healthy people of different races in public databases found that the presence or absence of some non-essential genes can increase susceptibility
to gastric cancer.
For example, the non-essential genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 were significantly more likely to be lost in gastric cancer populations than in other populations
.
For those new genes predicted by sequences other than the human reference genome, the research team used the long-read long sequences of the three-generation sequencing to conduct chromosomal localization research, and successfully localized the new gene GC0643 to the 9q34.
2 locus
.
The use of cell line model in vitro overexpression of GC0643 gene significantly inhibits tumor cell growth, migration invasion, cell cycle progression and promotes apoptosis, and this tumor suppressor effect can be reversed
by gene retraction.
The new gene GC0643 has been certified by the International NCBI Database (GenBank: MW194843.
1
).
Thesis Links:
reprints are welcome to be forwarded to the circle of friends and WeChat groups
