Shanghai Jiaotong University Nature sub-journal completed the pangenomic study of gastric tumors

Recently, the research group of Professor Wei Chaochun of the School of Life Science and Technology of Shanghai Jiao Tong University, the research group of Professor Yu Yingyan of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, the research group of Professor Chen Hongzhuan of the Shanghai Institute of Interdisciplinary Sciences of Shanghai University of Traditional Chinese Medicine, and the research group of Professor Zhang Zhen of the Affiliated Cancer Hospital of Fudan University jointly completed the pangenomic research on gastric tumors of Han people, and the related results paper "Pangenomic analysis of Chinese gastric cancer It was published online in the internationally renowned academic journal Nature Communications on September 15, 2022
.

Professor Yu Yingyan of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Professor Wei Chaochun of School of Life Science and Technology of Shanghai Jiao Tong University, Professor Chen Hongzhuan of the Institute of Interdisciplinary Sciences of Shanghai University of Traditional Chinese Medicine, and Professor Zhu Zhenggang of Ruijin Hospital are co-corresponding authors
of this article.

The human reference genome sketch published in 2001 is difficult to fully reflect the genomic diversity
of different regions and ethnic groups because its DNA samples are taken from a small number of donor individuals.

The study used HUPAN to analyze the whole genome depth sequencing data of 185 pairs of gastric cancer and paracancerous tissues (a total of 370 samples), and constructed a gastric cancer pangenome containing the human reference genome (GRCh38) and 80.
88 Mbp new
sequences.
Of these, the new sequence contains at least 14 new genes
.
The individual genomes are then compared with the pangenome as a reference to identify PAV
in the genomes of individuals with gastric cancer.
A total of 261 non-essential genes (genes that were missing or partially missing in one or more individuals) were found in gastric cancer populations, of which 195 non-essential genes belonged to genes common to both paracancerous and cancerous tissues (186 located on the human reference genome, 9 new sequence genes).

Comparing these non-essential 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 absent in gastric cancer populations than in other populations
.

For the new sequence of the non-reference genome, the research group successfully discovered the GC0643 gene that can be located to the chromosome 9q34.
2 locus by predicting the gene
structure and using long-read long sequencing data for chromosome localization.

Overexpression of GC0643 gene in vitro in cell lines significantly inhibits tumor cell growth, migration invasion, cell cycle progression and promotes apoptosis, and this tumor suppressor effect can be reversed
by gene retraction.
This suggests that sequences missing in the human reference genome may play a role
in the development of disease.

The research was supported
by the National Natural Science Foundation of China, the National Key R&D Program, the Shanghai Municipal Science and Technology Commission, the Shanghai Collaborative Innovation Center for Translational Medicine, the Medical and Engineering Interdisciplinary Innovation Fund of Shanghai Jiao Tong University, the Medical Research Fund of Shen Nanpeng Shanghai Jiao Tong University, and the Shanghai Jiao Tong University-Yale Cooperative Research Seed Fund.

Paper Link:_msthash="320081" _msttexthash="88634">Author:

Faculty of Life Science and Technology

Feeds:

Faculty of Life Science and Technology