RÉSUMÉ
In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53 genes. Between February 2017 and October 2020, 1460 samples from 1395 patients were analyzed. 1201 patients (86.1%) had at least one variant identified, most frequently TP53 (47.5%), KRAS (32.2%) or EGFR (24.2%). Among these, 994 patients (71.3%) had clinically relevant variants eligible for treatment with approved therapies or clinical trial enrollment. The incremental cost of NGS beyond single gene testing (EGFR, ALK) was CAD $233 per case. Reflex upfront NGS identified at least one actionable variant in more than 70% of patients with NSCLC, with minimal increase in testing cost. Implementation of NGS panels remains essential as treatment paradigms continue to evolve.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Séquençage nucléotidique à haut débit , Humains , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Mutation , Protéines proto-oncogènes p21(ras)/génétiqueRÉSUMÉ
PURPOSE: Each year, 17,000 new breast cancer cases are diagnosed in Argentina, and 5400 women die of breast cancer. The contribution of cancer-related mutations to the incidence of breast cancer in Argentina has not yet been explored. METHODS: We sequenced the entire coding regions of BRCA1, BRCA2, PALB2 and RAD51C in 112 unselected Argentinian breast cancer patients. RESULTS: A pathogenic genetic variant was found in 12 of 112 (10.7%) patients; two in BRCA1 (1.8%), five in BRCA2 (4.5%), four in PALB2 (3.6%) and one in RAD51C (0.9%). Three of four (75%) PALB2 mutation carriers carried the same variant (c.1653T > A). CONCLUSIONS: A founder mutation in PALB2 accounts for up to 4% of breast cancer patients in Argentina. BRCA1, BRCA2, PALB2 and RAD51C should be included in the genetic testing panel of breast cancer patients in Argentina.