Germline APC Mutations Are Not Commonly Seen in Children With Sporadic Hepatoblastoma

Abstract

Hepatoblastoma is the most common primary liver tumor in childhood and occurs more commonly in families with familial adenomatous polyposis. Germline mutations of the gene responsible for familial adenomatous polyposis--adenomatous polyposis coli (APC)--are described in patients with hepatoblastoma even without a family history. We investigated children presenting with apparently sporadic hepatoblastoma between 1991 and 2004. Blood samples were available from 29 children (18 boys) whose conditions were diagnosed at a median age of 22 months (range 6-119 months). No germline APC mutations were found, which does not support the need for routine screening in sporadic hepatoblastoma in the absence of a suggestive family history of colorectal cancer or suspicion of familial adenomatous polyposis.

Germline APC mutations in hepatoblastoma

“…Although several studies did not find evidence of pathogenic germline APC mutations in patients presenting with apparent sporadic HB, earlier studies indicated approximately 10% of children with HB have germline APC mutations in the absence of positive family history for FAP . Interestingly, the studies reporting no evidence of clinically consequential germline APC mutations in sporadic HB acknowledged the presence of silent APC point mutations (4/29 patients, 13%), and abnormal β‐catenin accumulation (15/21 patients, 71%) in their respective sporadic HB populations . It is possible that HB tumors with somatic beta‐catenin mutations will be found only in non‐FAP patients based on the notion that somatic beta‐catenin mutations and germline APC mutations are mutually exclusive in HB.…”

“…Additionally, accurate family history may not always be available, which could result in a failure to diagnose this genetic condition in a timely manner . Although several studies did not find evidence of pathogenic germline APC mutations in patients presenting with apparent sporadic HB, earlier studies indicated approximately 10% of children with HB have germline APC mutations in the absence of positive family history for FAP . Interestingly, the studies reporting no evidence of clinically consequential germline APC mutations in sporadic HB acknowledged the presence of silent APC point mutations (4/29 patients, 13%), and abnormal β‐catenin accumulation (15/21 patients, 71%) in their respective sporadic HB populations .…”

“…The gene responsible for FAP, adenomatous polyposis coli ( APC ), is located on chromosome 5q21. APC is a tumor suppressor gene involved in regulating levels of nuclear β‐catenin protein . The WNT/β‐catenin pathway affects liver development, regeneration, and tumorigenesis .…”

Hepatoblastoma in two siblings and familial adenomatous polyposis: causal nexus or coincidence?

“…They concluded that HB is the first manifestation of a de novo APC mutation in a substantial fraction of apparently sporadic HB and recommended routine APC mutation screening in these patients and colorectal surveillance thereafter. In contrast, in a study of Harvey et al [28] no germline APC mutations were found in 29 children with sporadic HB. However, the difference between the APC mutation detection rates in the two studies is not statistically significant [28] and further studies are needed before definite recommendations can be given.…”

“…In contrast, in a study of Harvey et al [28] no germline APC mutations were found in 29 children with sporadic HB. However, the difference between the APC mutation detection rates in the two studies is not statistically significant [28] and further studies are needed before definite recommendations can be given. Till then, the following procedure seems appropriate (Fig.…”