Table 3. Integrative sequencing provides an array of actionable observations.
Potentially actionable observations in a representative set of cases following integrative sequencing analyses highlights the spectrum of different kinds of aberrations including germline, somatic, and gene expression changes.
| Case | MO_1311 | TP_2132 | MO_1329 | MO_1233 | TP_2130 | MO_1102 | MO_1315 | MO_1331 | MO_1547 | MO_1177 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cancer | Renal Cell Carcinoma | Glioblastoma Multiforme | Chondrosarcoma | Adenoid Cystic Carcinoma | Sphenoid Sinus Squamous Cell Carcinoma | Thymic Carcinoma | Non-Small Cell Lung Cancer | Tongue Squamous Cell Carcinoma | Parotid Gland Cancer | Non-Small Cell Lung Carcinoma | |
| Gender/Age | M65 | M53 | F59 | F44 | M70 | M34 | F54 | F68 | F66 | M63 | |
| Germline | Germline_Pathogenic SNV/indels | FH p.K477 dup non-frameshift insertion | PMS2 p.R802* | - | - | - | MLH1 splicing mut. | - | - | - | - |
| Tumor exome/genome | Copy number_Amp | - | PDGFRA, KIT | - | - | - | - | - | MCL1, ARNT | MDM2, CDK4, CCND1 | PDGFA, BRD4 |
| Copy number_Del | - | PTEN | - | copy loss: CDKN1C, CDKN2A, CDKN2B, ARID1A, ARID1B, SMARCA2 | - | MLH1 copy loss | copy loss: CDKN2A, CDKN2B, SMARCA2, PTEN, TP53 | - | - | CDKN2A/2B | |
| SNV_gain of fn | - | - | IDH p.R132G | - | - | - | - | - | NOTCH1 p.L1678P, p.Q2444* (PEST domain) | - | |
| SNV_loss of fn | - | - | - | KDM6A pQ1311* (homozygous) | TP53 p.R273C, p.T125M | TP53 p.R282Q | TP53 p.S260T, KEAP1 p.R470H | IQGAP2 (G833*) | TP53 p.R175H | TP53 p.E285K; BAP1 p.W52* (homozygous) | |
| Indel_gain of fn | - | - | - | *NOTCH1 non-frameshift deletion (hotspot) activating | EGFR p.D770delinsDGF non-frameshift insertion | - | - | - | - | - | |
| Indel_loss of fn | - | PTEN | - | - | FAT1 p.T1818fs deletion | CDKN2A fs insertion | - | - | - | - | |
| Mutation signature | - | - | - | - | - | MSI Signature | - | - | MSI Signature | - | |
| Transcriptome | Gene Fusion | - | - | - | - | - | - | KIF5B-RET | - | - | NF2-OSBP2 (loss of NF2) |
| Gene Expression_Outlier | - | - | - | NOTCH1, FGFR2, ERBB3 | - | PD-L1 | - | MCL1, ARNT | - | PDGFA, BRD4 | |
| Gene Expression_Biomarkers | - | - | - | - | - | - | - | - | - | UPK3B, LRRN4, CALB2, WT-1, MSLN, PDPN | |
| Pathogens | Cancer Virus | - | - | - | - | - | - | HPV16 | - | - | |
| Clinical Action | FH p.K477dup is associated with Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). | TKIs such as Nilotinib/Ponatinib; Genetic Counselling | IDH inhibitors | Clinical trial with Notch inhibitor | Eligible for FDA-approved Cetuximab | PD-1/ PD-L1 targeting immunotherapy | Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer; NCT01639508 | T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers (NCT02280811) | Immunotherapy, NOTCH inhibitor, CDK4/6 inhibitor | Biomarkers supporting diagnosis of Mesothelioma. Clinical trial with BRD inhibitor (NCT01587703) | |
| Therapeutically actionable aberration | Diagnostically/prognostically actionable aberration | ||||||||||