Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.

EBioMedicine
David VenetChristos Sotiriou

Abstract

In breast cancer (BC), axillary lymph node (ALN) involvement is one of the strongest adverse prognostic factors. However, it is unclear whether loco-regional lymph node deposits are effectively the root of secondary metastases or only an indicator of competence of the primary tumour to spread to distant organs. Here, we investigated the evolutionary trajectories of primary tumour, ALN and distant metastasis samples from 16 estrogen-receptor (ER)-positive lymph node-positive BC patients. Low-pass whole genome sequencing was performed to infer somatic copy number aberrations and the phylogenetic profiles for all patients were obtained. We show that lymph nodes and distant metastases shared a common origin in only 25% of the cases highlighting that the predominant route of metastatic dissemination is the direct seeding of tumour cells from the primary tumour to distant organs, independently of lymph node metastasis. Noticeably, patients sharing a common origin significantly have worse prognosis. Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC. This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research ...Continue Reading

Citations

Nov 27, 2020·British Journal of Cancer·Alessandra I RiggioAlana L Welm
Apr 4, 2021·Cancer Discovery·Joan Massagué, Karuna Ganesh
May 28, 2021·The American Journal of Pathology·Samir JanaDennis Jones
Nov 13, 2021·Clinical & Experimental Metastasis·Stanley P LeongMarlys Witte

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Datasets Mentioned

BETA
EGAS00001004356

Methods Mentioned

BETA
surgical resection

Software Mentioned

CNVkit
ABSOLUTE
CNT
BWA aligner
Picard

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