Whole-Exome Sequencing Identifies Frequent AHNAK2 Mutations With Prognostic Significance in Undifferentiated Primary Liver Carcinoma.
AHNAK2 mutation, found in 68% of these liver tumors, predicts shorter survival
Whole-Exome Sequencing Identifies Frequent AHNAK2 Mutations With Prognostic Significance in Undifferentiated Primary Liver Carcinoma.
Undifferentiated primary liver carcinoma (undifferentiated primary liver carcinoma) is an exceedingly rare hepatic malignancy lacking hepatocytic or cholangiocytic differentiation, and its clinicopathologic and molecular characteristics remain poorly defined.
With AHNAK2 -mutated undifferentiated primary liver carcinoma had significantly shorter overall survival, elevated tumor mutational burden (tumor mutational burden), and markedly reduced infiltration of CD4⁺, CD8⁺, CD20⁺, and CD68⁺ immune cells.
We retrospectively analyzed 25 undifferentiated primary liver carcinoma cases from a single Chinese institution over an 8-year period and performed whole-exome sequencing (whole-exome sequencing) to delineate the genomic landscape, combined with multiplex immunofluorescence (mIF), routine histopathology, and immunohistochemistry (immunohistochemistry) for phenotypic assessment.
Compared with conventional hepatocellular carcinoma (hepatocellular carcinoma) from the Cancer Genome Atlas (TCGA), undifferentiated primary liver carcinoma demonstrates a distinct mutational profile, with frequent alterations in 5 key oncogenic pathways (Hippo, NOTCH, WNT, RTK-RAS, and TP53) in 96.0% of cases and a higher mutation frequency of core pathway genes than hepatocellular carcinoma.
These findings support the recognition of undifferentiated primary liver carcinoma as a clinically aggressive and molecularly distinct entity and indicate that the AHNAK2 mutation may serve as a potential prognostic biomarker in this rare malignancy.