Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?

Hepatoblastoma (HB) is the most frequent liver tumor in childhood, occurring in the first few years of life. Surgery combined with chemotherapy has resulted in dramatic improvements in prognosis. However, even today, about one quarter of affected children do not survive the disease. Compared to the general population, the risk of HB is 750-7,500 times higher in children predisposed to familial adenomatous polyposis (FAP), an autosomal-dominant cancer predispostion syndrome caused by germline mutations in the tumor suppressor gene APC. Only limited data exist about the frequency of APC germline mutations in cases of apparently sporadic HB without a family history of FAP. In our sample of 1,166 German FAP families, all known cases of HB were registered. In addition, 50 patients with apparently sporadic HB were examined for APC germline mutations. In the FAP families, seven unrelated cases of HB are documented; three had been detected at an advanced stage. In patients with apparently sporadic HB, germline mutations in the APC gene were identified in 10%. These data raise the issue of the appropriate screening for HB in children of FAP patients. To date, the efficiency of surveillance for HB is unclear. In Beckwith-Wiedemann syndrome (BWS), recent studies suggest an earlier detection of both Wilms tumor and HB by frequent screening. We discuss the rationale and implications of a screening program; besides the examination procedure itself, screening for HB in children of FAP patients would have important consequences for the policy of predictive testing in FAP. In a substantial fraction of sporadic HB, the disease is obviously the first manifestation of a de novo FAP. These patients should be identified by routine APC mutation screening and undergo colorectal surveillance thereafter.

Aretz S ，Koch A ，Uhlhaas S ，Friedl W ，Propping P ，von Schweinitz D ，Pietsch T ... -  《PEDIATRIC BLOOD & CANCER》

Germline APC mutations are not commonly seen in children with sporadic hepatoblastoma.

Harvey J ，Clark S ，Hyer W ，Hadzic N ，Tomlinson I ，Hinds R ... -  《-》

Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.

Brueckl WM ，Ballhausen WG ，Förtsch T ，Günther K ，Fiedler W ，Gentner B ，Croner R ，Boxberger F ，Kirchner T ，Hahn EG ，Hohenberger W ，Wein A ... -  《DISEASES OF THE COLON & RECTUM》

Molecular analysis of the APC gene in 105 Dutch kindreds with familial adenomatous polyposis: 67 germline mutations identified by DGGE, PTT, and southern analysis.

van der Luijt RB ，Khan PM ，Vasen HF ，Tops CM ，van Leeuwen-Cornelisse IS ，Wijnen JT ，van der Klift HM ，Plug RJ ，Griffioen G ，Fodde R ... -  《HUMAN MUTATION》

Mutation analysis of the adenomatous polyposis coli (APC) gene in northwest Spanish patients with familial adenomatous polyposis (FAP) and sporadic colorectal cancer.

Germline mutations in the tumor-suppresor APC gene are associated with hereditary familial adenomatous polyposis (FAP) and somatic mutations are common in sporadic colorectal cancer. In this study, we report the identification of three novel germline mutations: 1682-1683insA, 3252-3253insAT, 3544A>T and a new somatic mutation 4130-4131delTT, all giving rise to truncated APC proteins. The majority of the mutations we found originate a truncated APC protein and cause the FAP phenotype. However, special attention must be given to the missense mutations Asp1822Val and Ser2621Cys since their segregation with the FAP phenotype is questionable. In our FAP families we did not find any genetical alterations at codon 1309, being this mutation the most frequent reported in APC. Differences in the recurrence of pathological mutations in APC could exist among populations. However, epidemiological studies must be performed to confirm this hypothesis.

Ruiz-Ponte C ，Vega A ，Carracedo A ，Barros F ... -  《-》