Candidate target genes for loss of heterozygosity on human chromosome 17q21

Abstract

Loss of heterozygosity (LOH) on chromosome 17q21 has been detected in 30% of primary human breast tumours. The smallest common region deleted occurred in an interval between the D17S746 and D17S846 polymorphic sequences tagged sites that are located on two recombinant P1-bacteriophage clones of chromosome 17q21: 122F4 and 50H1, respectively. To identify the target gene for LOH, we defined a map of this chromosomal region. We found the following genes: JUP, FK506BP10, SC65, Gastrin (GAS) and HAP1. Of the genes that have been identified in this study, only JUP is located between D17S746 and D17S846. This was of interest since earlier studies have shown that JUP expression is altered in breast, lung and thyroid tumours as well as cell lines having LOH in chromosome 17q21. However, no mutations were detected in JUP using single-strand conformation polymorphism analysis of primary breast tumour DNAs having LOH at 17q21. We could find no evidence that the transcription promoter for JUP is methylated in tumour DNAs having LOH at 17q21. We suspect that the target gene for LOH in primary human breast tumours on chromosome 17q21 is either JUP and results in a haploinsufficiency for expression or may be an unidentified gene located in the interval between D17S846 and JUP.

Polymorphisms in the Janus kinase 2 (JAK)/signal transducer and activator of transcription (STAT) genes: putative association of the STAT gene region with familial breast cancer

“…The darker the colour, the higher the LD: black coloured squares indicate a very strong LD. (De Marchis et al 2004, Maguire et al 2005. Our results add important information to this wellcharacterised allelic imbalance data on chromosome 17q by indicating a role of individual's genotype on BC susceptibility.…”

Spinophilin loss contributes to tumorigenesis in vivo

“…Spn is located in close proximity to NME1, only 1 Mb away, and likely shares the allelic loss observed in previous studies of NME1. [27][28][29] Furthermore, cytogenetic studies that have investigated the genetic linkage of breast and ovarian cancers to chromosome 17q have revealed the existence of a tumor suppressor gene distal to BRCA1, 19,20 specifically in hereditary breast and breast-ovarian familial cancer, [30][31][32] indicating the importance of this locus in the pathology of cancer.…”

Clinico-pathological significance of the molecular alterations of the SPOP gene in prostate cancer

“…SPOP is located in the 17q21 locus which has been described to be a region with a high allelic imbalance in primary tumours [7]. Structurally, SPOP consists of an N-terminal MATH domain that recruits substrate proteins and a C-terminal BTB (Bric-a-brac/Tamtrack/Broad complex) domain that interacts with Cul3.…”