Table 4.
Therapeutical intervention based on the genetic alterations identified with comprehensive genetic profiling.
| Tumour type | Genetic alterations | TMB status | Therapy | Treatment duration (month) and reason of termination | |
|---|---|---|---|---|---|
| On-label therapy | |||||
| Metastasis of HGSOC | BRCA1 p.Glu23ValfsTer17, c.68_69delAG,X | low | PARP inhibitor | 14 | Progression |
| Colon carcinoma | KRAS p.Ala146Thr, c.436G > A | highX | Immunotherapy | 60 | On therapy |
| Metastasis of HGSOC | BRCA1 p.Gln1604AsnfsTer2, c.4806delTX and LOH of BRCA1, BRCA2, BARD1, BRIP1, POLD1, POLE | low | PARP inhibitor | 6 | Progression |
| HGSOC | LOH: BRCA1X, BRIP1, CDK12, PALB2, POLD1, POLE, PTEN, RAD51B, RAD51C, RAD51D, RAD54L | failed | PARP inhibitor | 5 | Toxicity |
| Lung carcinoma | MET amplificationX and LOH of POLD1 | highX | MET TKI (Crizotinib) and immunotherapy | 4 | Progression |
| Large cell lung neuroendocrine carcinoma | LOH: CHEK2, NBN, POLD1, PPP2R2A, PTEN | high X | Immunotherapy | 8 | On therapy |
| Breast carcinoma | Amplification of BRCA2 exons: 2–11X | low | PARP inhibitor | 4 | On therapy |
| Metastasis of melanoma | Deletion of BRCA2 exons 15–16 and exons 19–20; NRAS exon 3: p.Gln61Leu, c.182A > T, | highX | Immunotherapy | 4 | Toxicity |
| Ovarian adenocarcinoma | LOH: BRCA1 X, BRIP1, CDK12, PALB2, POLD1, RAD51C, RAD51D, RAD54L | low | PARP inhibitor | 5 | On therapy |
| Rectum carcinoma | APC p.Tyr935Ter, c.2805C > A and del NCOR1, CDKN2A, ERAP2 | highX | Immunotherapy | 1 | Death |
| Metastasis of endometrial carcinoma | MSH6 exon 9, p.Arg1331Ter, c.3991C > TX, deletions: HLA-B, HLA-A, ERAP2 | low | Immunotherapy | 1 | Death |
| Off-label therapy | |||||
| Cholangiocarcinoma | LOH: BRCA2X, POLE, PPP2R2A | low | PARP inhibitor | 11 | Progression |
| Metastasis of breast cancer | dup: BRCA1X, BRCA2X and LOH: ATM, CHEK1, PPP2R2A, RAD51B | low | PARP inhibitor | 1 | Toxicity |
| Small cell lung cancer | LOH: BRCA2X, CHEK2, PTEN, RAD54L; BRCA1, BRCA2 | low | PARP inhibitor | 4 | Progression |
| Metastasis of thymoma | LOH: RAD51BX | low | PARP inhibitor | 4 | On therapy |
| High-grade sarcoma | LOH: BRCA1,X BRCA2, ATM, BARD1, CHEK1, CHEK2, PPP2R2A, RAD51B | low | PARP inhibitor | 2 | Progression |
| Malignant peripheral nervous sheet tumor (MPNST) | deletion BRCA2 exons 10–27X | low | PARP inhibitor | 5 | Progression |
| Testicular embrional carcinoma | amplification METX | low | cabozantinib | 6 | Progression |
| Parathyroid carcinoma | deletion: CDKN2A, HLA-A, ERAP2 | highX | immunotherapy | 11 | On therapy |
| Leiomyosarcoma (rectosigma) | LOH: BRCA2X, ATM, CHEK1, CHEK2, POLE, PPP2R2A | low | PARP inhibitor | 8 | Progression |
| High-grade spindle cell sarcoma | LOH: BRCA1X, BRCA2, ATM, BRIP1, CDK12, CHEK1, NBN, PALB2, POLE, PPP2R2A, PTEN, RAD51B, RAD51C, RAD51D | low | PARP inhibitor | 1 | Progression |
| Metastatic germcell tumor | LOH: BRCA1X, ATM, BARD1, BLM, CHEK1, FANCL | low | PARP inhibitor | 6 | On therapy |
| Metastasis of leiomyosarcoma | deletion BRCA2 exon 16–20 X | low | PARP inhibitor | 1 | Toxicity |
| Metastasis of postpubertal teratoma | LOH: BARD1X, CHEK2 | low | PARP inhibitor | 2 | Progression |
TMB: tumor mutation burden;
X
: indicates the genetic alteration representing an indication for therapy.