Inactivating mutations and hypermethylation of the <i>NKX2‐1/TTF‐1</i> gene in non‐terminal respiratory unit‐type lung adenocarcinomas

Summary

This molecular study characterised genetic and epigenetic alterations of the NKX2-1/TTF-1 gene in non-TRU-type lung adenocarcinomas, identifying it as a significantly mutated gene (16.3% of cases) with exclusive association to a TTF-1-negative/HNF4-α-positive adenocarcinoma subtype. Eight distinct NKX2-1/TTF-1 mutations were functionally validated as loss-of-function events, and hypermethylation of the gene body was found in TTF-1-negative cases, suggesting both genetic and epigenetic inactivation mechanisms drive aberrant differentiation in this adenocarcinoma subtype.

UK applicability

This is a molecular oncology study with no direct applicability to UK agricultural, soil health, or food systems. It may inform UK clinical practice for lung cancer diagnosis and prognosis, but lies outside Vitagri's Pulse Brain focus.

Key measures

Frequency of TP53, KRAS, and NKX2-1/TTF-1 mutations (%; 43 cases); NKX2-1/TTF-1 mutation types (frameshift, nonsense, missense); TTF-1 and HNF4-α immunohistochemistry expression patterns; NKX2-1/TTF-1 gene body methylation status by bisulfite sequencing

Outcomes reported

The study identified NKX2-1/TTF-1 mutations and hypermethylation patterns in 43 non-terminal respiratory unit-type lung adenocarcinomas using whole-exome sequencing and functional assays. It characterised the association between genetic and epigenetic inactivation of NKX2-1/TTF-1 and specific adenocarcinoma morphologies and immunohistochemical profiles.

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