Journal article
Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR
Hepatology (Baltimore, Md.), Vol.57(1), pp.120-130
01/2013
DOI: 10.1002/hep.26004
PMID: 22899566
Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers and is the third leading cause of cancer‐related death. There is a universal estimated male/female ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Sex bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored sex differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both sexes and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB‐induced liver tumors from male mice (10/10, 100%) but infrequent in female mice (2/9, 22%). Human single‐nucleotide polymorphism data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression–based Poly7 subclass patients were predominantly male (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02), and this subclass was accompanied by EGFR overexpression (P < 0.001). Conclusion: Sex bias occurrence of HCC associated with EGFR was confirmed in experimental animals using the SB transposon system in a reverse genetic approach. This study provides evidence for the role of EGFR in sex bias occurrences of liver cancer and as the driver mutational gene in the Poly7 molecular subclass of human HCC. (HEPATOLOGY 2013)
Details
- Title: Subtitle
- Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR
- Creators
- Vincent W KengDaniela SiaAaron L SarverBarbara R TschidaDanhua FanClara AlsinetManel SoléWai L LeeTimothy P KukaBranden S MoriarityAugusto VillanuevaAdam J DupuyJesse D RiordanJason B BellKevin A T SilversteinJosep M LlovetDavid A Largaespada
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.57(1), pp.120-130
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- DOI
- 10.1002/hep.26004
- PMID
- 22899566
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Number of pages
- 11
- Language
- English
- Date published
- 01/2013
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025481802771
Metrics
12 Record Views