Background
Methods
Clinical samples collection
Genomic DNA extraction
DIPS-PCR
Sequencing
Mapping of viral and cellular sequences in viral-cellular junctions
Extract of gene lists around HPV integration sites
GO enrichment analysis of gene lists
Protein interaction network analysis
Hi-C data analysis
Results
Overview of viral-cellular junctions in 13 patients infected with HPV16
Sample name | Age (years) | Pathology | Number of validated viral-cellular junctions |
---|---|---|---|
S1-2 | 41 | SCC | 1 |
S2-25 | 45 | HSIL | 2 |
C3-64 | 45 | HSIL | 1 |
C4-77 | 32 | HSIL | 1 |
C5-87 | 49 | HSIL | 2 |
S6-95 | 48 | SCC | 1 |
C7-35 | 44 | Normal | 0 |
C8-7 | 51 | HSIL | 0 |
S9-10 | 38 | SCC | 0 |
S10-11 | 43 | SCC | 0 |
C11-60 | 28 | HSIL | 0 |
C12-67 | 42 | SCC | 0 |
C13-75 | 35 | LSIL | 0 |
Architectures of 8 viral-cellular junctions
Junction ID | Type | Left element location | Middle element location | Right element location | Overlapping |
---|---|---|---|---|---|
S1-2:J-01 | Type 2 | HPV16 E1(211 bp) | NA | chr3:175701251-175701313 (63 bp) NAALADL2
| Left & Right: No overlapping |
S2-25:J-03 | Type 1 | HPV16 E1(122 bp) | chr9:125080078-125080338(261 bp) SCAI
| chr4:148216738-148216850 (159 bp) NR3C2
| Left & Middle: GATGCA Middle & Right: GATC |
S2-25:J-04 | Type 1 | HPV16 E1(185 bp) | chr17:30708288-30708380(93 bp) | chr1:165472779-165473100(322 bp) | Left &Middle: No overlapping Middle & Right: AGATC |
C3-64:J-05 | Type 2 | HPV16 E2(325 bp) | NA | chr3:124457727-124457915 (189 bp) KALRN
| Left & Right: AA |
C4-77:J-06 | Type 2 | chr4:185352615-185352687 SNX25(72 bp) | NA | HPV16 L1(310 bp) | Left & Right: No overlapping |
C5-87:J-07 | Type 2 | chr22:34824077-34824170(93 bp) | NA | HPV16 L1(224 bp) | Left & Right: CAATA |
C5-87:J-08 | Type 1 | chr22:34819634-3481983 (201 bp) | chrX:109333446-109333511(66 bp) | HPV16 E5 (299 bp) | Left & Middle: GTGG Middle & Right: GTGTT |
S6-95:J-09 | Type 2 | HPV16 E1(239 bp) | NA | chr16:82782336-82782494 (159 bp) CDH13
| Left & Right: CTGCAA |
Cellular genes directly overlapping with viral-cellular junctions
Cellular genes located around HPV16 integration sites
GOterm | Description |
P-value | FDR q-value |
---|---|---|---|
GO:0010528 | Regulation of transposition | 1.37E-07 | 1.92E-03 |
GO:0002548 | Monocyte chemotaxis | 6.18E-07 | 2.88E-03 |
GO:0071346 | Cellular response to interferon-gamma | 1.47E-06 | 5.14E-03 |
GO:0034341 | Response to interferon-gamma | 4.00E-06 | 1.12E-02 |
GO:0070383 | DNA cytosine deamination | 1.47E-05 | 3.44E-02 |
Common fragile sites located around HPV16 integrating sites
Junction ID | Integrating location | Nearest CFSs |
---|---|---|
S1-2:J-01 | 3q26.31 | FRA3C(3q27) |
S2-25:J-03 | 9q33.3 and 4q31.22 | FRA9E(9q32) and FRA4C(4q31.1) |
S2-25:J-04 | 17q11.2 and 1q23.3 | FRA17A(17q23) and FRA1G(1q25) |
C3-64:J-05 | 3q21.2 | FRA3F(3q22) |
C4-77:J-06 | 4q35.1 | FRA4C(4q31.1) |
C5-87:J-07 | 22q12.3 | FRA22B(22q12.2) |
C5-87:J-08 | 22q12.3 and Xq23 | FRA22B(22q12.2) and FRAXD(Xq27) |
S6-95:J-09 | 16q23.3 | FRA16D(16q23) |
Chromosome translocation around HPV16 integration sites
HPV affected cancer-related genes documented in Dr.VIS v2.0 database
ID | Method | Disease | Subtype | Cytoband | Nearest gene |
---|---|---|---|---|---|
DRVIS03185 | PCR | HNC | HPV16 | 1q25 |
TNFSF4
|
DRVIS03195 | Exome-Seq | CC | HPV56 | 3q28 |
TP63
|
DRVIS03198 | Mapping | CC | HPV16 | 1p36.32 |
TP73
|
DRVIS02845 | RS-PCR | CC | HPV16 | 4q13.3 |
RASSF6
|
DRVIS00089 | DIPS-PCR | CC | HPV16 | 2q21.2 |
ARHGEF4
|
DRVIS00246 | DIPS-PCR | CC | HPV16 | 16q24 |
CDH13
|