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Novel CD44 messenger RNA isoforms in human thyroid and breast tissues feature unusual sequence rearrangements
G Ermak1, T Jennings, A Boguniewicz
1Departments of Medicine and Pathology, Albany Medical College, Albany, New York 12208, USA.
Abstract:
CD44 is a family of cell surface proteins implicated in adhesion interactions and tumor metastasis. Multiple CD44 mRNA isoforms arise from alternative splicing of variant exons (termed v1-v10). We recently discovered a novel CD44 mRNA isoform in human papillary thyroid cancers featuring a junction between subsegments of exons 4 and 13 (v8). The sequence ACAG was repeated at both the donor and acceptor sites in the genomic DNA (G. Ermak et al., Cancer Res., 56: 1037-1042, 1996). We used reverse transcription-PCR to characterize expression of this isoform in a panel of thyroid lesions. In addition, we assayed three cryopreserved human breast cancers and two samples of normal breast tissue (from female subjects who had undergone cosmetic mammoplasty) to determine whether a similar isoform is present in breast carcinomas. Levels of the novel isoform were up-regulated in 88% of the goiters, adenomas, and papillary cancers, but were undetectable in cases of thyroiditis and absent or low-level in four samples of normal thyroid tissue. The three breast cancers each yielded a 546-bp PCR product that was not detected in normal breast tissue. The PCR product from one of the breast cancers was cloned, and sequence analysis revealed a novel mRNA isoform featuring a junction between exon 3 and an internal site within exon 13 (v8). The sequence GCTTCAG was repeated at both the donor and acceptor sites in the genomic DNA. These results show that human thyroid and breast tissues contain novel CD44 mRNA isoforms featuring unusual rearrangements at repeated sequences. Further studies are warranted to determine whether the expression of this class of isoforms correlates with growth status.
Insights
Researchers found new CD44 mRNA variants in thyroid and breast cancers. These novel isoforms, linked to cancer growth, show unusual genetic rearrangements and warrant further study.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- CD44 is a cell surface protein family involved in cell adhesion and tumor metastasis.
- Alternative splicing of CD44 mRNA generates multiple isoforms, including variant exons v1-v10.
Purpose of the Study:
- To investigate novel CD44 mRNA isoforms in human thyroid and breast cancers.
- To characterize the expression and genomic basis of these isoforms.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect and analyze CD44 mRNA isoforms.
- Cloning and sequence analysis were performed on PCR products from breast cancer samples.
Main Results:
- A novel CD44 mRNA isoform (v8) with a junction between exon 4 and exon 13 was identified in human papillary thyroid cancers.
- This novel isoform was upregulated in 88% of goiters, adenomas, and papillary thyroid cancers, but not in thyroiditis or normal thyroid tissue.
- A similar novel CD44 mRNA isoform, with a junction between exon 3 and exon 13, was detected in human breast cancers but not in normal breast tissue.
Conclusions:
- Human thyroid and breast tissues harbor novel CD44 mRNA isoforms with unique rearrangements at repetitive DNA sequences.
- The discovery of these isoforms suggests a potential role in cancer development and progression.
- Further research is needed to determine if the expression of these CD44 isoforms correlates with tumor growth status.