Table 2. WGS and RNA sequencing analyses... | American Society of Hematology

Table 2.

WGS and RNA sequencing analyses

WGS results
Expected findings if HCC was caused by rAAV direct integration	Expected findings if HCC was not caused by rAAV direct integration	Observed findings
Integration of vector sequences in or near known oncogenes.	Common HCC mutations (eg, TP53 or NFE2L2).²¹	WGS provided a genome coverage of 120× and 107× for the HCC and HCC-adjacent sample, respectively.
	No AAV ISs near oncogenes.	WGS identified 3 additional ISs in the HCC and 2 in the HCC-adjacent sample.
		No IS was identified in >1 read, indicating a low IS rate in the liver and a lack of a dominant IS in the HCC sample.
		Independent of etranacogene dezaparvovec treatment there were the following mutations:Mutations in TP53, NFE2L2, and PTPRKLarge chromosomal rearrangements in chromosomes 1, 8, and X, characteristic of HCC
		In addition, vector integration events occurred at a low rate and in genomic sites not known to be associated with HCC.
RNA sequencing transcriptome profiling
Not described.	Differential expression of genes previously identified in HCC.	RNA transcripts identified that are among the most consistently differentially expressed in HCC (arising independent of AAV), including COL1A1, LCN2, AEBP1, and CRP.

WGS results
Expected findings if HCC was caused by rAAV direct integration	Expected findings if HCC was not caused by rAAV direct integration	Observed findings
Integration of vector sequences in or near known oncogenes.	Common HCC mutations (eg, TP53 or NFE2L2).²¹	WGS provided a genome coverage of 120× and 107× for the HCC and HCC-adjacent sample, respectively.
	No AAV ISs near oncogenes.	WGS identified 3 additional ISs in the HCC and 2 in the HCC-adjacent sample.
		No IS was identified in >1 read, indicating a low IS rate in the liver and a lack of a dominant IS in the HCC sample.
		Independent of etranacogene dezaparvovec treatment there were the following mutations:Mutations in TP53, NFE2L2, and PTPRKLarge chromosomal rearrangements in chromosomes 1, 8, and X, characteristic of HCC
		In addition, vector integration events occurred at a low rate and in genomic sites not known to be associated with HCC.
RNA sequencing transcriptome profiling
Not described.	Differential expression of genes previously identified in HCC.	RNA transcripts identified that are among the most consistently differentially expressed in HCC (arising independent of AAV), including COL1A1, LCN2, AEBP1, and CRP.

AEBP1, Ae binding protein 1; COL1A1, α-1 type I collagen; CRP, C-reactive protein; LCN2, lipocalin-2.

For more detailed results, please see supplemental Material.