The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Solid Tumors 441
chromosome band 11q13 (160–164). Further, oncocytomas lack the 3p deletions seen in clear cell/
granular or chromophobe renal cell carcinomas, which are the histologies generally considered in
their differential diagnosis.
Wilms Tumor
Wilms tumors are the most common type of renal cancer in children. They typically contain primitive
blastemal cells that differentiate into epithelial tubular and/or mesenchymal populations. The
classic “triphasic” Wilms tumor contains an admixture of these blastemal, epithelial, and mesenchymal
components, and all three cell types can contain the same clonal chromosome aberrations (165).
There is no one cytogenetic aberration found across the board in Wilms tumors, but various aberrations
are found individually in at least 10% of cases. These include trisomies 6, 8, 12, and 18 and
deletions of 11p13, 11p15, and 16q (see Table 2) (137,166,167).
Deletion of 11p13 is the most extensively characterized cytogenetic aberration in Wilms tumors.
This aberration became the focus of many studies after reports that individuals with the WAGR
(Wilms tumor with aniridia, genitourinary malformations, and retardation) syndrome often had constitutional
deletions at chromosome band 11p13. The Wilms tumor suppressor gene (WT1) is deleted
in WAGR syndrome. This gene has been cloned and characterized (168) and appears to play a critical
role in urogenital development (168,169). However, the WAGR phenotype results from deletions of
several genes, with the WT1 gene deletion responsible for predisposition to Wilms tumors and deletion
of a neighboring gene, PAX6, responsible for aniridia (170). Although most or all WAGRassociated
Wilms tumors have complete inactivation of WT1, such inactivation is found in fewer than
20% of sporadic Wilms tumors.
Various cytogenetic features are associated with anaplastic histologic features in Wilms tumor.
Complex karyotypes with chromosome counts in the triploid to tetraploid range are generally found
in tumors with either diffuse or focal anaplasia (171). Similarly, Wilms tumors with p53 tumor suppressor
gene mutations generally have some degree of anaplasia (172).
Mesoblastic Nephroma
Mesoblastic nephromas are the most common renal tumors diagnosed in neonates, but are rarely
encountered in older children. The histology of mesoblastic nephroma is varied. Those composed of
bland, benign-appearing, spindle cells are known as “classic” (173), whereas those with more cellularity,
mitoses, and necrosis are known as “cellular” mesoblastic nephroma (174). Trisomy 11 is a
consistent cytogenetic aberration in mesoblastic nephromas and is generally found only in the “cellular”
histology cases (90,175). Approximately 70% of cellular mesoblastic nephromas contain trisomy
11, often accompanied by trisomies for chromosomes 8 and 17 (90). By contrast, clonal
chromosome aberrations have not been identified in classic histology mesoblastic nephromas. These
findings suggest that trisomy 11, with or without other clonal chromosome aberrations, is associated
with progression from classic to cellular histology in mesoblastic nephroma. Mesoblastic nephromas
with trisomy 11 generally also contain a balanced translocation, t(12;15)(p13;q26), resulting in oncogenic
fusion of the ETV6 and NTRK3 genes. t(12;15)(p13;q26) is difficult to detect using standard
chromosome banding methods, but it is readily demonstrable by FISH. These cytogenetic associations
have been useful diagnostically, because Wilms tumors (which are the entity most often confused
with mesoblastic nephroma) rarely have trisomy 11 and have not been found to have the (12;15)
translocation (166,167).
BREAST CANCER
Most breast cancers have complex karyotypes, and traditional cytogenetic analysis is not performed
generally in the routine diagnostic evaluation of breast cancer. However, several cytogenetic
amplifications, particularly those targeting the MYC and ERBB2 (HER-2/neu) genes, have assumed
prominence in the prognostic and therapeutic evaluation of breast cancer patients. Both MYC and