PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 8073225

Human imprinted genes as oncodevelopmental markers.

H Biran·I Ariel·N de Groot·A Shani·A Hochberg
View original source ↗Export metadata ↓

Abstract

Imprinted genes mediate unique maternal or paternal genetic roles and their function is essential in prenatal development. The reciprocally imprinted human insulin-like growth factor 2 (IGF2) and H19 genes are expressed during embryonal life, also in the placenta, and are downregulated postnatally. They reexpress in pediatric tumors (e.g. Wilms' tumor) and in inborn developmental syndromes predisposing to such tumors (e.g., Beckwith-Wiedemann syndrome). H19 (RNA transcripts) and IGF2 are manifested in Wilms' tumor, rhabdomyosarcoma, immature ovarian teratoma and gestational trophoblastic diseases. We have found that in the placenta and in urothelial carcinoma, H19 expression reflects the degree of invasiveness. These genes, displaying a tissue-specific oncofetal pattern of expression, are, therefore, tumor markers.

Explore related subjects

Beckwith-Wiedemann SyndromeChildChromosomes, Human, Pair 11Embryonic and Fetal DevelopmentFemaleFetusGenetic MarkersHumansInsulin-Like Growth Factor IIKidney NeoplasmsMaleNeoplasmsOvarian NeoplasmsPlacentaPregnancyRhabdomyosarcomaTeratomaTrophoblastic NeoplasmsWilms TumorJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H Biran, I Ariel, N de Groot, A Shani, A Hochberg. 1994. Human imprinted genes as oncodevelopmental markers.. https://doi.org/10.1159/000217882

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2002

Feasibility of partial nephrectomy for Wilms' tumor in children with Beckwith-Wiedemann syndrome who have been screened with abdominal ultrasonography.

BACKGROUND: Children with Beckwith-Wiedemann syndrome (BWS), a congenital syndrome associated with Wilms' tumor commonly are screened with abdominal sonography resulting in detection of tumor at a lower stage. Wilms' tumors have been traditionally treated with complete nephrectomy; however, smaller tumors are amenable to nephron-sparing surgery. Because Wilms' tumors may be metachronous and nonmalignant disease may compromise renal function in BWS, nephron-sparing approaches may be desirable as the first option. METHODS: Seven patients with BWS and Wilms' tumor underwent nephrectomy. The preoperative computed tomography (CT) or ultrasound scan were evaluated by a pediatric surgeon to assess whether partial nephrectomy would have been feasible. The determining criteria included tumor involving one third or less of the kidney and no involvement of either hilar or vascular structures. RESULTS: Seven patients underwent complete nephrectomies. The remaining patient, who had undergone a left nephrectomy before the initiation of screening had salvage chemotherapy after biopsy results showed right kidney involvement with Wilms' tumor. CONCLUSIONS: Nephron-sparing surgery is reasonable to consider in children with Beckwith-Wiedemann syndrome who are screened at intervals of 4 months or less. The relative benefits of partial nephrectomy for children with Wilms' tumor-predisposing conditions only can be assessed in the setting of a cooperative clinical trial.

Beckwith-Wiedemann Syndrome↗
PubMed2002

Recent advances in Wilms tumor genetics.

The past decade has witnessed substantial growth in our knowledge of the genes and loci that are altered in Wilms tumor. Although Wilms tumor was one of the original paradigms of Knudson's two-hit model of cancer formation, it has become apparent that several genetic events contribute to Wilms tumorigenesis. Recent research has identified targets and regulators of the first Wilms tumor gene, WT1, has uncovered several candidate genes at the second Wilms tumor locus, WT2, and has identified two familial Wilms tumor loci, FWT1 and FWT2. The recent discovery of activating beta-catenin mutations in some Wilms tumors has also implicated the Wnt signaling pathway in this neoplasm. Recurrent abnormalities of other loci, including 16q, 1p, and 7p, have indicated that these sites may harbor Wilms tumor genes. An enhanced understanding of these and other genetic lesions will provide the foundation for novel targeted Wilms tumor therapies.

Beckwith-Wiedemann Syndrome↗
PubMed2001

Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1.

Dysregulation of imprinted genes on human chromosome 11p15 has been implicated in Beckwith-Wiedemann syndrome (BWS), an overgrowth syndrome associated with congenital malformations and tumor predisposition. The molecular basis of BWS is complex and heterogeneous. The syndrome is associated with alterations in two distinct imprinting domains on 11p15: a telomeric domain containing the H19 and IGF2 genes and a centromeric domain including the KCNQ1OT1 and CDKNIC genes. It has been postulated that disorders of imprinting in the telomeric domain are associated with overgrowth and cancer predisposition, whereas those in the centromeric domain involve malformations but not tumor development. In this study of 125 BWS cases, we confirm the association of tumors with constitutional defects in the 11p15 telomeric domain; six of 21 BWS cases with uniparental disomy (UPD) of 11p15 developed tumors and one of three of the rare BWS subtype with hypermethylation of the H19 gene developed tumors. Most importantly, we find that five of 32 individuals with BWS and imprinting defects in the centromeric domain developed embryonal tumors. Furthermore, the type of tumors observed in BWS cases with telomeric defects are different from those seen in BWS cases with defects limited to the centromeric domain. Whereas Wilms' tumor was the most frequent tumor seen in BWS cases with UPD for 11p15 or H19 hypermethylation, none of the embryonal tumors with imprinting defects at KCNQ1OT1 was a Wilms' tumor. This suggests that distinct tumor predisposition profiles result from dysregulation of the telomeric domain versus the centromeric domain and that these imprinting defects activate distinct genetic pathways for embryonal tumorigenesis.

Beckwith-Wiedemann Syndrome↗