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One of the most commonly mutated genes in lung cancer turns out to come in two kinds: one that destroys the protein and carries the worst prognosis, and one that leaves it intact. Both do worse than average, and both do better than average on immunotherapy.
Genomic, protein expression and clinical outcome data were analysed for patients with SMARCA4-altered lung cancer treated at one centre. Among 4,813 patients with non-small-cell lung cancer, 407, 8%, carried a SMARCA4 alteration. Two categories were described: class 1 (truncating mutations, fusions and homozygous deletion) and class 2 (missense mutations). Loss of protein expression was associated with class 1 alterations, 81% against 0%. Both classes co-occurred more frequently with KRAS, STK11 and KEAP1 mutations than in SMARCA4 wild-type tumours. In metastatic disease, SMARCA4 alterations were associated with shorter overall survival, with class 1 the shortest. Treatment with immune checkpoint inhibitors was associated with improved outcomes in SMARCA4-altered tumours, with class 1 responding best.
It turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.
Shares Gregory J. Riely, STK11 / KEAP1 co-mutations, KEAP1, STK11.
Shares Gregory J. Riely, STK11 / KEAP1 co-mutations, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, T-cell exhaustion.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, T-cell exhaustion.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, T-cell exhaustion.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, T-cell exhaustion.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, KRAS.
Shares STK11 / KEAP1 co-mutations, KEAP1, STK11, KRAS.