Table 1.

Associations between CIN and tumor initiation and metastases

Cancer type	Event	Methodology	Phenomenon and potential mechanism	Refs.
Breast cancer	SCNAs	Profiling of 52 single cells from a primary basal breast tumor and 48 cells from the tumor's associated liver metastasis	• A high level of concordance was observed at the level of SCNAs	(109)
			• Tumors grew by punctuated clonal expansions with few persistent intermediates
		Comparing somatic mutations and gene CNAs of primary breast cancers and their matched metastases from patients with estrogen receptor (ER)-negative breast cancer	• There was a large subset of gene CNAs (55%) and nonsynonymous somatic mutation sharing between primary tumors and paired metastases	(110)
			• Synchronous metastases displayed higher concordance with the paired primary tumor than did metachronous metastases
			• The repertoires of somatic genetic alterations in ER-negative breast cancer metastases may differ from those of their primary tumors
		Investigating the genomic evolution between primary and matched metastatic ER+ breast cancers after failure of adjuvant treatment	• ESR1 mutations were in the metastases, but none were in the primary tumor	(111)
			• Although there was a high level of concordance between primary tumor and matched metastases for the investigated molecular alterations, ESR1 mutations as potential actionable targets were identified only in metastases
		Performing DNA exome and RNA-sequencing of matched primary tumors and multiple metastases from 83 distinct specimens of 16 patients	• Genetic drivers unique to metastasis were identified as somatic mutations in the androgen and ER genes	(112)
			• Most metastatic drivers might be established in the primary tumor despite the substantial heterogeneity observed in the metastases
		High-depth whole-exome sequencing of distinct core biopsies of primary breast cancers and synchronous distant metastases	• Synchronous primary breast cancers and metastases differed in their repertoire of somatic genetic alterations	(113)
			• Mutational signature shifts could affect spatial intratumoral genetic heterogeneity
		Genome-wide sequencing of ctDNA from plasma of 162 patients with biopsy-proven metastatic triple-negative breast cancer (TNBC)	• Percent genome altered and copy-number profiles were similar between primary tumor and metastases in TNBCs	(114)
			• SCNAs were enriched in TNBC metastases
		Whole-exome sequencing (WES) of a base-like breast cancer primary tumor and a metachronous brain metastasis	• More than 90% of the SCNAs in the primary tumor were propagated in metastases, whereas ~80% of SCNAs in metastases were not shared by the primary tumor	(115)
			• Enhanced CNAs were in metastases
Prostate cancer	SCNAs	Comparing analysis of 333 primary prostate cancers (represented by single biopsies) and an unrelated cohort of 150 soft tissue and bone metastases from castration-resistant prostate cancers	• There was a remarkably higher SCNA and mutational burden in the metastases than in primary tumors	(68)
			• Patients who had a high SCNA burden had an elevated risk of relapse
	TP53 mutations	Whole-genome and ultradeep targeted sequencing of longitudinally collected metastatic and primary tumors	• Both primary tumor and metastatic clones were detected	(116)
			• Enrichment of TP53 mutations was present in metastases
		WES of multiple metastases arising from prostate tumors in 10 patients	• Metastasis-to-metastasis seeding may occur either by a branching or a linear pattern of spread	(117)
Colorectal cancer		Combing WES CNAs for 15 triplets	• The primary colorectal carcinomas and about half the metastatic colorectal carcinomas had the same clonal origin	(118)
		Whole-genome sequencing of two primary colorectal cancer tumors and their metastases	• Most of the somatic alterations existed in both sites, and distinct clonal evolution patterns were identified in the two cases	(119)
		Performing targeted next-generation sequencing on liver metastases and primary tumors from 18 patients with liver-limited metastatic colorectal cancer	• There was high genomic concordance between metastases and primary tumors, in support of the linear progression model in liver-limited metastatic colorectal cancer	(120)