Next-Generation Sequencing (NGS) in cancer is a high-throughput, molecular diagnostic method that simultaneously sequences millions of DNA/RNA fragments to identify genetic alterations (mutations, fusions, deletions) within tumors. It enables precise, personalized oncology by analyzing actionable mutations, guiding targeted therapy, and monitoring disease recurrence
- TP53– most frequently mutated gene pan-cancer (~40% overall). Extremely high in high-grade serous ovarian cancer (~95%); very common in head and neck squamous cell carcinoma (HNSCC), esophageal, lung squamous, and basal-like breast.
- – Mutated in ~40% of all cancers.
- – Found in almost every solid tumor type (ovarian, breast, lung, colorectal, head & neck, esophageal, liver, etc.).
- – Acts as a universal genomic guardian→ loss leads to genomic instability.
- KRAS– dominant in pancreatic ductal adenocarcinoma (>90%); common in colorectal (~35–45%) and lung adenocarcinoma (~25–35% in Western cohorts). Ras pathway mutated in ~19% of all cancers.
- – KRAS / NRAS / HRAS (RAS family)
- – Frequently mutated in pancreatic, colorectal, lung, thyroid, melanoma, bladder cancers.
- – RAS mutations = constitutive activation of MAPK pathway.
- PIK3CA– frequent in breast (esp. HR+ luminal A/B ≈45%/29%) and endometrioid endometrial cancer (~40–70%); also present in head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC).
- – Altered inbreast, endometrial, head & neck, colorectal, bladder, cervical
- – Activates PI3K/AKT/mTOR signaling (growth/survival).
- APC– gatekeeper of colorectal tumorigenesis; mutated in roughly ~80% of colorectal cancers.
- – Dominant in colorectal cancer, but mutations also seen in gastric and pancreatic tumors
- BRAF– ~40–60% of cutaneous melanomas (mostly V600E/K), ~40–60% papillary thyroid carcinoma, ~8–12% colorectal cancers.
- – Most famous inmelanoma, thyroid, colorectal, but appears in others at lower frequency.
- – Part of the RAS–RAF–MAPK pathway.
- EGFR– lung adenocarcinoma: ≈10–15% in European/North American populations, up to ~50% in East Asians; enriched in never-smokers and females.
- – Mutated or amplified inlung, breast, gastric, glioblastoma.
- – Targetable with monoclonal antibodies and TKIs.
- CTNNB1 (β-catenin)– hepatocellular carcinoma (~25–30%); also enriched in endometrioid endometrial cancers
- – Common in liver, endometrial, desmoid tumors, present in others.
- PTEN – common tumor suppressor loss in endometrioid endometrial cancer (~55–80% altered) and present in a substantial subset of glioblastoma; also altered in prostate cancer.
- IDH1– hallmark of lower-grade glioma (LGG) and secondary glioblastoma multiforme (GBM) (~70–80% of LGG; ~10% of GBM overall).
- – IDH1/2 not pan-cancer at high frequency, but found in gliomas, intrahepatic cholangiocarcinoma, some sarcomas.
- MYC (amplification)
- – Common driver in breast, lung, ovarian, liver, colorectal.
- – Regulates proliferation and metabolism.
