Loss of heterozygosity on chromosome 16 in sporadic Wilms' tumour

Abstract

Summary To establish whether loss of heterozygosity (LOH) for chromosome 16q in Wilms' tumours confers an adverse prognosis, DNA from 40 Wilms' tumour/normal pairs were analysed using highly polymorphic microsatellite markers along the length of 1 6q. Fifteen per cent of tumours showed LOH for 16q. Although the common region of allele loss spanned the 16q24-qter region, a second distinct region of LOH was identified in 16q21. (Coppes et al. 1992: Maw et al. 1992: Grundy et al. 1994: Austruy et al. 1995: Redeker et al 1996. Using a panel of informative markers for the region 16ql2.2-qter. Maw et al (1992) were the first to demonstrate LOH for 16q in 9 (20%c) of 45 informatiVe patients by Southem blot analysis. A larger follow--on study. as part of NWTS4. involving 232 patients. found a similar frequency of LOH at 17%7. but used only polymorphic markers that mapped to the distal 16q22-qter region (Grundv et al. 1994). In the study by Coppes et al (1992). using only two polymorphic markers mapping to 16q22.2 and 16q24.3. LOH was identified in 20% of tumours. The most recent studv. albeit in a relatively small group of patients (Austruy et al. 1995). found the highest level of LOH (25%7c) using a large panel of restriction length polymorphisms and microsatellite probes. Furthermore. LOH for 16q has been associated with a worse outcome because these patients have a relapse rate 3.3 times higher than those with tumours retaining heterozygosity for 16q (Grundy et al 1994).Because cytogenetic and molecular studies of Wilms' tumours clearly suggest a role for grenes on 16q in the molecular pathology of this tumour. we have undertaken LOH analysis for 16q markers using a large. well-characterized series of sporadic Wilms' tumours. Our results clearly show that LOH is relatively frequent in Wilms' tumours. especially in patients with an adverse outcome. MATERIALS AND METHODSDNA was prepared from tumour tissue and lymphocNies using standard phenol-chloroform extraction procedures described by Wadey et al (1990). The optimal polymerase chain reaction (PCR) conditions

Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

“…No specific gene mutation has yet been identified as a direct contributor to their pathogenesis. Wilms tumor is known to have allelic loss at numerous loci (Grundy et al, , 1998Law et al, 1997;Klamt et al, 1998;Natrajan et al, 2006). One Wilms tumor gene (WT1) has been identified and mapped to 11p13 (Call et al, 1990;Gessler et al, 1990).…”

Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

“…Chromosome 16q23 LOH has been described in a range of cancer types (Tsuda et al, 1990;Sato et al, 1991;Latil et al, 1997;Grundy et al, 1998). We previously reported high frequencies of deletions within 16q23 in human breast carcinomas, both in primary tumors (61%), local recurrences (62%) and distant metastases (83%) (Driouch et al, 1998).…”

“…Studies on recurrent somatic genetic alterations in human tumors have led to the identi®ca-tion of several`cancer genes' which have been suggested to be involved in the initiation and/or progression of breast cancer (Bieche and Lidereau, 1995). One of the most frequent aberrations detected in breast cancer as well as in other cancers (hepatocellular carcinoma, ovarian and prostatic cancers, Wilms' tumors, myeloid malignancies and central nervous system primitive neuroectodermal tumors) is loss of heterozygosity (LOH) on the long arm of chromosome 16 (Tsuda et al, 1990;Sato et al, 1991;Latil et al, 1997;Grundy et al, 1998).…”

Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

“…CnABP overexpression was indeed highest in WT samples with a LOH at chromosomal arms 16q and 11p, with overexpression in 70% and 100%, respectively. As LOH at 16q has been associated with later stages of tumor progression and poor prognosis (7,8) and typically follows loss of Wt1 at 11p15 (48), the overexpression of CnABP likely comes as a later event in tumor progression. The 2-to 18-fold overexpression of CnABP in 16q LOH tumors is especially remarkable in that the CnABP gene is located on this chromosomal segment (16q24).…”

“…However, 15% to 20% of WT patients experience relapse associated with resistance to treatments and poor prognosis (3,4). An increased probability of relapse and mortality correlates with anaplasia and metastasis (5,6) as well as increased chromosomal anomalies (7,8). At the molecular level, relapse has been linked to consistent deregulation of a limited number of genes, including components of the calcineurin signaling pathway (9).…”