Molecular cytogenetic analysis of consistent abnormalities at 8q12-q22 in breast cancer

Abstract

Studies using comparative genomic hybridization (CGH) indicate that portions of chromosome arm 8q from 8q12 to 8qter are present at an increased relative copy number in a broad range of solid tumors. In this study we define an ∼ 1 Mb wide region that appears to be frequently abnormal in copy number or structure in breast cancer cell lines and primary tumors. This was accomplished by fluorescence in situ hybridization (FISH) with yeast artificial chromosomes (YACs) mapped to 8q12‐q22. Eleven breast cancer cell lines and ten primary tumors were analyzed. A minimal region of rearrangement was localized to the CEPH‐YAC 928F9 in three breast cancer cell lines with unbalanced translocation breakpoints mapping in this region. Unbalanced translocations also were detected in two primary tumors mapping between CEPH‐YAC clones 890C4 and 936B3, flanking 928F9. An increased copy number in the minimal region was detected in nine cell lines and in multiple primary tumors. This suggests the possibility that a single gene mapping to 928F9 is involved in breast cancer development or progression and may be deregulated by copy number increases in some tumors and by translocation in others. Four expressed sequence tags were mapped to YAC 928F9 and analyzed for rearrangements by Southern analysis and for abnormal expression by Northern analysis. Genes Chromosomes Cancer 22:105–113, 1998. © 1998 Wiley‐Liss, Inc.

The hD52 (TPD52) gene is a candidate target gene for events resulting in increased 8q21 copy number in human breast carcinoma

“…The hD52 locus was mapped with respect to a YAC contig map spanning regions of an 8q12–q22 breast cancer amplicon (Schoenberg Fejzo et al, 1998) to determine whether hD52 is consistently included in chromosomal aberrations encompassing this region. The hD52 gene was localized using PCR to YAC 936B3, found at 102 cM on chromosome 8 (Schoenberg Fejzo et al, 1998).…”

“…The hD52 locus was mapped with respect to a YAC contig map spanning regions of an 8q12–q22 breast cancer amplicon (Schoenberg Fejzo et al, 1998) to determine whether hD52 is consistently included in chromosomal aberrations encompassing this region. The hD52 gene was localized using PCR to YAC 936B3, found at 102 cM on chromosome 8 (Schoenberg Fejzo et al, 1998). In this previous study, YAC 936B3 was shown to map within the amplicon peak at 8q12–q22 in the human breast cancer SK‐BR‐3 cell line, and distal to the translocation breakpoints identified in the breast cancer cell lines MCF7, BT‐474, and MDA‐MB‐361 (Schoenberg Fejzo et al, 1998).…”

“…To investigate whether hD52 represents a target gene, the gene was fine‐mapped with respect to a previously established yeast artificial chromosome (YAC) contig map of an 8q12–q22 breast cancer amplicon (Schoenberg Fejzo et al, 1998). Transcript levels were subsequently compared in four human breast carcinoma cell lines with or without numerically defined chromosomal gains including hD52 (Kallioniemi et al, 1994; Schoenberg Fejzo et al 1998). Human D52 gene dosage and protein expression were also compared in breast carcinoma tissues.…”

Rac signaling in breast cancer: A tale of GEFs and GAPs

“…The PREX2 gene is located in a chromosomal region that has been linked to aggressive cancer and metastatic progression and is frequently amplified in breast and prostate cancers [147, 148]. Interestingly, analysis of a breast tumor dataset annotated for PI3K pathway alterations revealed a positive association between P-Rex2a and PTEN expression.…”

JAB1/CSN5: a new player in cell cycle control and cancer

“…The JAB1/CSN5 locus is located on chromosome 8q13.1, a region that is frequently amplified in breast, prostate, colorectal and ovarian cancers [73-77], which has also been linked to aggressive cancer phenotypes and metastatic progression [10,78]. …”