Genomic Evolution of Breast Cancer Metastasis and Relapse

By L. Yates, S. Knappskog, David C. Wedge, J. R. Farmery, Santiago Gonzalez, Iñigo Martincorena, Ludmil B. Alexandrov, P. van Loo, H. K. Haugland, P. Lilleng and 20 more. Cancer Cell, 2017

605 citations recorded by the source corpus.

Summary Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/c3947b9e04d7058bfee329cf13b04c849b0b227c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. K. Guan
2. J. Reis-Filho
3. K. Polyak

In Molecular Biology

1. K. Guan
2. J. Reis-Filho
3. K. Polyak
4. J. Baselga
5. Nikolaus Schultz
6. Larry Norton
7. Ronglai Shen
8. Sumit Middha

In Pathology and Forensic Medicine

1. K. Guan
2. J. Reis-Filho

Citations in the corpus

• The Hippo signalling pathway and its implications in human health and diseases (2022, background): “245,246 in YAP-de fi cient PyMT mice, which is a breast cancer model, the incidence of lung metastasis was reduced.”
• The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers (2018, background): “These studies have shown that while metastases are clonally related to their primary tumor, they nonetheless often acquire driver genomic alterations not present in the primary disease including mutations that inactivate the SWI-SNF and JAK2-STAT3 pathways (Yates et al., 2017).”
• Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis (2018, background): “A recent study examined the genomic evolution of breast cancer metastasis and relapse of the 299 samples from 170 patients with locally relapsed or metastatic breast cancer, and found that metastasis or relapse disseminated late from primary tumors, and continued to acquire mutations.(340) As a resu”
• Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment (2019, background): “Phylogenetic analysis has the potential to distinguish local recurrences from second primary tumors and to help determine the origin of a metastatic lesion in a patient with a history of independent primary tumors (131).”
• Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal (2018, neutral): “Our observations contrast the divergent lymph node/distant metastasis patterns reported in other tumor types (Brastianos et al., 2015; Yates et al., 2017), and are consistent with the frequent presentation of lymph node metastases with visceral metastases, and the lack of therapeutic benefit from…”