Genome And Transcriptome Feature Of Breast Cancer Metastasis Subclone And Its Mechanism Of Collective Intravasation

Metastasis is the major cause of breast cancer death.Although the predilection sites,pathways and molecular mechanism have been well studied,little is known about how genomic changes affect molecular regulations in breast cancer metastasis.There is no any approach that could effectively control breast cancer metastasis yet.Recently,with the breakthrough of single-cell(or microcell)sequencing technology,it becomes possible to evaluate the genomic and signaling pathway heterogeneity in tumors.Our research is based on multi-region microcell laser capture microdissection(LCM)sampling.By specific collecting 17 adjacent normal tissue cells,17 primary tumor cells,20 intravasating tumor cells and 36 distant metastasis tumor cells and 7 lymphocytes cell culsters,then applying parallel genome and transcriptome sequencing(G&T seq)to these samples,we can explore the mechanism of breast cancer metastasis through a multi-omics angle.By analyzing the genome structure of metastasis subclones,we found,in genome copy number variation area,some lymph node metastasis cell clusters only have a chrXq arm amplification,which indicated that only a small change will be enough for lymph node metastasis.On the other hand,a highly genome stability may be benefit for cell clusters intravasation to vessel.In transcriptome spectrum,we identify there exists three distinct metastasis paths in one patient.We detailed dedicated the enrichment pathways of the significant changing genes in the metastasis paths and discover the hub genes of biological control network.By combining the genome and transcriptome map,we think a chromosome instability combined with the changing of the tumor suppression gene,will promote the cell cluster intravasation to blood vessel.The hub genes controlling this network included AIK2,H2B/a and CDKN2.In the aspect of lymph node metastasis,we think the changing of MMP family genes and ribosome genes will leads to district genome feature of metastasis cell clusters.Hub genes controlling these two networks including GELB,S15 a etc.We hope our research can fill the gap of describing breast cancer metastasis subclone genome feature and lay a theoretical foundation for developing new therapies to control hematogenous dissemination of breast cancer.