Good news! Cancer is history (soon)!
The author of this article, i.e. Krista Conger appears very clever! She used the terms woman/women only once in the entire article, but used the term patient 9 times. Is this some sort of a kowtow to LGBTQ?
"Breast cancers can be classified into subgroups that hint at the aggressiveness of the cancer and the likelihood that the patient will experience a recurrence years after their initial diagnosis.
Now researchers ... have shown that these subgroups can be bundled into three main groups based on structural variations in their DNA – including repeats, or amplifications, of cancer-associated genes called oncogenes on chromosomes and the presence of small DNA circles untethered to the rest of the genome. These variations are established early during cancer development and are maintained as the disease advances and metastasizes. ...
This robust classification system could also differentiate breast cancer patients who are most likely to benefit from aggressive early intervention from those who may be able to safely defer such aspects of treatment. ..."
From the abstract:
"Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors—
oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)
—is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities.
Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER+ subtypes with increased risk of relapse decades after diagnosis.
Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
We demonstrate that breast tumours fall along a continuum constrained by three genomic archetypes.
The ER+ high-risk integrative subgroup is characterized by complex focal amplifications, similar to HER2+ tumours, including cyclic extrachromosomal DNA amplifications induced by ER through R-loop formation and APOBEC3B-editing, which arise in pre-invasive lesions.
By contrast, triple-negative tumours exhibit genome-wide instability and tandem duplications and are enriched for homologous repair deficiency-like signatures, whereas ER+ typical-risk tumours are largely genomically stable.
These genomic archetypes, which replicate in an independent cohort of 2,659 primary tumours, are established early during tumorigenesis, sculpt the tumour microenvironment and are conserved in metastatic disease. These complex structural alterations contribute to replication stress and immune evasion, and persist throughout tumour evolution, unveiling potential vulnerabilities."
Complex rearrangements fuel ER+ and HER2+ breast tumours (open access)
Fig. 1: ENiClust identifies the IC subtypes.
Fig. 5: Genomic and microenvironmental evolution of breast cancer subgroups.
No comments:
Post a Comment