Background
Methods
Patients and pathological materials
DNA extraction, library preparation, and targeted sequencing
Identification of somatic variants from targeted sequencing
Whole-genome sequencing
WGS data analysis and somatic mutation detection
Copy number variant detection
RNAseq analysis and identification of differentially expressed genes
Specimen preparation and tandem mass spectrometry proteomics
Results
Identification of somatic mutations by targeted sequencing
Patient ID | Diagnosis | Stage | Vital status at last follow-upa | Age at diagnosis (years) | Overall survival or length of follow-up (years) | Mutation(s) detected |
---|---|---|---|---|---|---|
LGS101 | LGSOC | IIIC | Deceased | 54 | 5.1 | BRAF p.V600E |
LGS102 | LGSOC | IIIC | Alive with disease | 51 | 14.3 | KRAS p.G12A |
LGS103 | LGSOC | IIIC | Alive (NED) | 66 | 8.3 | KRAS p.Q61H |
LGS104 | LGSOC | lllB | Deceased | 59 | 4.5 | KRAS p.Q61L |
LGS105 | LGSOC | IIIC | Deceased | 52 | 4.4 | TP53 p.R342P |
LGS106 | LGSOC | lllC | Deceased | 66 | 6.9 | UBR5 p.E312A |
LGS107 | LGSOC | IIIB | Deceased | 56 | 1.4 | |
LGS108 | LGSOC | lllC | Deceased | 72 | 1.9 | |
LGS109 | LGSOC | lllC | Deceased | 26 | 12.0 | |
LGS110 | LGSOC | lllC | Deceased | 59 | 0.2 | |
LGS111 | LGSOC | IV | Deceased | 21 | 2.1 | |
LGS112 | LGSOC | IIIC | Alive with disease | 63 | 15.2 | |
LGS113 | LGSOC | IIIC | Deceased | 41 | 7.3 | |
LGS114 | LGSOC | IIIC | Deceased | 70 | 1.9 | |
LGS115 | LGSOC | IIIC | Deceased | 22 | 4.3 | |
LGS116 | LGSOC | IIIC | Alive (NED) | 73 | 11.6 | |
LGS117 | LGSOC | IIIC | Alive with disease | 45 | 14.9 | |
LGS118 | LGSOC | IIIC | Deceased | 64 | 11.2 | |
LGS119 | LGSOC | IIIC | Deceased | 20 | 17.1 | EPHA3 p.K761N; ATRX p. E481D |
LGS120 | LGSOC | IIIC | Alive with disease | 41 | 9.4 | |
LGS121 | LGSOC | IIIC | Deceased | 40 | 5.5 | |
LGS122 | LGSOC | IIIA | Deceased | 38 | 8.3 | |
SBOT101 | SBOT | IIC | Alive (NED) | 48 | 6.0 | |
SBOT102 | SBOT | IB | Alive (NED) | 49 | 5.6 | BRAF p.V600E |
SBOT103 | SBOT | IIB | Alive (NED) | 48 | 5.3 | BRAF p.V600E |
SBOT104 | SBOT | IA | Alive (NED) | 65 | 5.4 | BRAF p.V600E |
SBOT105 | SBOT | IIIC | Alive (NED) | 19 | 5.2 | BRAF p.V600E |
SBOT106 | SBOT | IIIC | Deceased | 59 | 6.6 | FBXW7 p.R505C |
Whole-genome sequencing
Copy number changes in LGSOC
RNAseq analysis
Symbol | Entrez gene name | Fold Change (long/short) | p-value | Short-term mean expression (TPM) | Long-term mean expression (TPM) | Location | Type(s) | Drug(s) |
---|---|---|---|---|---|---|---|---|
RKCG | Protein kinase C gamma | − 4.82 | 0.01 | 3.86 | 0.77 | Cytoplasm | Kinase | Go6983, ingenol mebutate, Ro31-8220 |
VAMP1 | Vesicle associated membrane protein 1 | − 1.97 | 0.00017 | 15.31 | 7.77 | Cytoplasm | Transporter | Botulinum toxin type B |
PER1 | Period circadian regulator 1 | − 1.82 | 0.0087 | 79.62 | 43.96 | Nucleus | Transcription regulator | Avibactam |
MKNK1 | MAPK interacting serine/threonine kinase 1 | − 1.75 | 0.0081 | 10.27 | 5.89 | Cytoplasm | Kinase | BAY1143269, dacomitinib, ETC-1907206, QL-X-138, SEL201, tomivosertib |
RPS6KA1 | Ribosomal protein S6 kinase A1 | − 1.7 | 0.0022 | 25.9 | 15.24 | Cytoplasm | Kinase | LJH685, PMD-026 |
POLE | DNA polymerase epsilon, catalytic subunit | − 1.59 | 0.01 | 11.9 | 7.53 | Nucleus | Enzyme | Bortezomib/cladribine/rituximabcin interferon |
HIF1A | Hypoxia inducible factor 1 subunit alpha | 1.96 | 0.0083 | 62.38 | 122.14 | Nucleus | Transcription regulator | EZN 2968, PX 478 |
SLC1A1 | Solute carrier family 1 member 1 | 3.86 | 0.01 | 1.18 | 4.54 | Plasma Membrane | Transporter | Riluzole |
Master regulator | Molecule type | Participating regulators | Predicted activation | Activation z-score | p-value of overlap | Target molecules in dataset |
---|---|---|---|---|---|---|
BHLHE40 | Transcription regulator | BHLHE40 | Activated | 2.236 | 0.0129 | HIF1A, LPAR1, PER1, PNRC1, SLC7A2 |
HNRNPK | Other | CEBPB, ERK1/2, HNRNPK, MAP2K1/2, SRC | Activated | 2.333 | 0.00606 | CTSV, FOXO1, HIF1A, HMGB2, KLF5, MKNK1, MXD3, NASP, POLE |
TCF4 | Transcription regulator | TCF4 | Inhibited | − 2 | 0.0333 | FOXO1, HIF1A, PPIH, RPS6KA1 |
USP4 | Peptidase | Akt, JINK1/2, P38 MAPK, SMAD4, USP4 | Inhibited | − 2.121 | 0.0119 | FOXO1, HIF3A, KLF5, LPAR1, NRP2,PPP1R1B,SMAD3,TPM2 |
USP9X | Peptidase | ITCH, PRKCB, SMAD4, USP9X, ZAP70 | Inhibited | − 2.646 | 0.00801 | ELOVL5, FOXO1, HIF1A, LPAR1, NASP, SMAD3,TPM2 |
Global proteomic analysis
Accession | Protein | Gene | MDACC long VS short (Log2 fold-change) | INOVA long VS short (Log2 fold-change) |
---|---|---|---|---|
P02144 | MYG_HUMAN Myoglobin | MB | 1.28 | − 1.11 |
Q9Y617 | SERC_HUMAN Phosphoserine aminotransferase | PSAT1 | 0.93 | 1.66 |
Q969H8 | MYDGF_HUMAN Myeloid-derived growth factor | MYDGF | 0.83 | 0.89 |
Q15645 | PCH2_HUMAN Pachytene checkpoint protein 2 homolog | TRIP13 | 0.66 | 1.14 |
Q9UBP6 | TRMB_HUMAN tRNA (guanine-N(7)-)-methyltransferase | METTL1 | 0.56 | 0.76 |
Q9Y657 | SPIN1_HUMAN Spindlin-1 | SPIN1 | 0.49 | 0.56 |
Q9Y4Z0 | LSM4_HUMAN U6 snRNA-associated Sm-like protein LSm4 | LSM4 | 0.48 | 0.79 |
Q9H0H5 | RGAP1_HUMAN Rac GTPase-activating protein 1 | RACGAP1 | 0.48 | 1.10 |
Q9ULW3 | ABT1_HUMAN Activator of basal transcription 1 | ABT1 | 0.45 | 0.67 |
P35269 | T2FA_HUMAN General transcription factor IIF subunit 1 | GTF2F1 | 0.41 | 0.66 |
Q9UBD5 | ORC3_HUMAN Origin recognition complex subunit 3 | ORC3 | 0.40 | 0.89 |
Q5T749 | KPRP_HUMAN Keratinocyte proline-rich protein | KPRP | 0.36 | − 1.57 |
P14373 | TRI27_HUMAN Zinc finger protein RFP | TRIM27 | 0.36 | 0.86 |
P25205 | MCM3_HUMAN DNA replication licensing factor MCM3 | MCM3 | 0.34 | 1.20 |
Q8NBM8 | PCYXL_HUMAN Prenylcysteine oxidase-like | PCYOX1L | − 0.54 | 0.79 |
O75506 | HSBP1_HUMAN Heat shock factor-binding protein 1 | HSBP1 | − 0.56 | − 0.85 |
P25445 | TNR6_HUMAN Tumor necrosis factor receptor superfamily member 6 | FAS | − 0.71 | − 0.85 |
Q9BQE5 | APOL2_HUMAN Apolipoprotein L2 | APOL2 | − 0.81 | − 0.96 |
P69905 | HBA_HUMAN Hemoglobin subunit alpha | HBA1 | − 0.95 | − 0.99 |
P68871 | HBB_HUMAN Hemoglobin subunit beta | HBB | − 1.03 | − 1.27 |