Table 2.

Prognostic value of aneuploidy, polyploidy and CIN.

method of determining ploidy/CIN	method actually reflects	tumor type	n	type of survival	__ year survival	survival rate for:		ref
						stable diploid	altered ploidy/ CIN
DNA content (aneuploidy and polyploidy)
DNA image cytometry- SSIa	proliferative index + heterogeneity	breast	154	overall	2–3	98%	74%	[75]
			890	overall	10	~90%	~65%	[54]
flow cytometry	# and location of all DNA peaks	breast	1391	relapse-free	10	~80–95%	~60–75%	[87]
	not specified	STSb	102	metastasis-free	5	77%	48%	[88]
	multiple stemlinesc		46	overall	15	~55%	~20%	[89]
nuclear grading	nuclear aread	lunge	133	recurrence-free	5	90%	58%	[90]
	largest nuclear diameterd		133	recurrence-free	5	89%	62%
genomic index	segmental gains & losses by CHG/# chromosomes involved	STSb (GIST)f	60	metastasis-free	5	93%	16%	[78]
FISH (cellular heterogeneity or CIN)
FISH (centromeres for Chr 3, 10, 11 & 17)	heterogeneity of 4 chromosomes	lunge	50	overall	4	~75%	~35%	[91]
FISH (EGFR-7p12, MYC-8q24, 5p15, 6cen, p16–9p21	heterogeneity of ≥ 4 chromosomes		47	overall	5	77%	33%	[92]
	heterogeneity of ≥ 3 chromosomes		63	overall	5	94%	69%	[53]
abnormal anaphases (lagging chromosomes and chromatin bridges)
lagging/bridge chromosomes	chromosome missegregation	lymphomag	54	overall	10	~65	~45	[23]
gene signatures
CIN70 and CIN25 gene signaturesh	structural aneuploidy and proliferation	6 typesi	1944	overall (breast cohort)	10	~70	~55	[76]
12 gene genomic instability signaturej	proliferative index/SSIa	breast	469	overall	5	~70–90%	~40–60%	[52]
				metastasis-free		~60–80%	~30–50%
		lunge	637	overall	5	~50–60%	~10–40%	[93]
		ovarian	124	relapse-free	10	~65%	~15%
67 gene CINSARC signaturek	combination of structural aneuploidy, proliferation and tumor grade	STSb	127	metastasis-free	5	75–84%	35–48%	[94]
		STSb (GIST)f	32	metastasis-free	5	100%	61%
					10	100%	30%
		breast	373	metastasis-free	10	~75–80%	~35–60%
		lymphomag	278	overall	10	~65–75%	~35–40%
Aurora A expression	AURKA mRNA level	STSb (GIST)f	60	metastasis-free	5	100%	38%	[78]
						100%	12%
112 CIN gene signaturel	Loss of heterozygosity	colon	548	disease-free	5	~95%	~75%	[95]

^aStemline Scatter Index (SSI) is the percentage of cells in S phase + the percentage of cells > 5c + coefficient of variation (standard deviation/mean). S

phase percentage contributes most to SSI.

^bSoft tissue sarcoma.

^c”Tumors were considered aneuploid when a distinct separate second or more G₀/G₁

peak(s) was present”.

^dbased on H&E staining.

^eNon-Small Cell Lung Cancer.

^fGastrointestinal Stromal Tumor.

^gDiffuse large B-cell lymphoma.

^hTo identify the CIN70 and CIN25 gene signatures, the authors inferred aneuploidy based on gene expression data. They then confirmed that in NCI60 cell lines, this correlates with structural aneuploidy as measured by SKY and SNPchip DNA copy number. Tumors with low versus high aneuploidy were compared to identify the 25 or 70 genes with the highest CIN score (designated CIN25 and CIN70). 43/70=61% of CIN70 genes are cell cycle regulated [77].

ⁱThe CIN25 signature is prognostic in 1 lung, 5 breast, 1 mesothelioma, 3 glioma, 1 medulloblastoma and 1 lymphoma cohort, but not in 3 lung, 1 ovarian, 1 lymphoma and 1 prostate cohort.

^jThe 12 gene signature was identified by analyzing gene expression data from 48 primary breast carcinomas stratified into 17 diploid genomically stable, 15 aneuploid genomically stable, and 16 aneuploid genomically unstable tumors by SSI. Only Aurora A overlaps with the CIN70 genes.

^kCINSARC (Complexity INdex in SARComa) genes were identified by comparing expression differences between 1) tumors with CGH imbalances of <20 with >35; 2) grade 3 vs grade 2 tumors; 3) CIN70 signature.

^lThe 112 CIN gene signature was identified by determining the LOH status in 745 tumors using 9 microsatellite markers representing 4 chromosome arms. An LOH ratio of 33% was used to separate CIN high from CIN low tumors. 25 CIN high and 10 CIN low tumors were used to identify the 112 gene signature. These 112 genes are non-overlapping with the CIN70.