Virgilio L, Shuster M, Gollin S M, Veronese M L, Ohta M, Huebner K, Croce C M
Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107, USA.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9770-5. doi: 10.1073/pnas.93.18.9770.
To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC cell lines for deletions within the FHIT locus by Southern analysis, for allelic losses of specific exons FHIT by fluorescence in situ hybridization (FISH) and for integrity of FHIT transcripts. Three cell lines exhibited homozygous deletions within the FHIT gene, 55% (15/25) showed the presence of aberrant transcripts, and 65% (13/20) showed the presence of multiple cell populations with losses of different portions of FHIT alleles by FISH of FHIT genomic clones to interphase nuclei. When the data obtained by FISH and by reverse transcriptase-PCR analyses are combined, 22 of 26 cell lines showed alterations of at least one allele of the FHIT gene. Our data indicate that the FHIT gene is disrupted in HNSCCs and hence, loss of FHIT function may be important in the development and/or progression of head and neck cancers.
为了确定位于3p14.2的FHIT基因在头颈部鳞状细胞癌(HNSCC)中是否发生改变,我们通过Southern分析检测了26种HNSCC细胞系中FHIT基因座内的缺失情况,通过荧光原位杂交(FISH)检测了特定外显子FHIT的等位基因缺失情况,并检测了FHIT转录本的完整性。3种细胞系在FHIT基因内表现出纯合缺失,55%(15/25)显示存在异常转录本,65%(13/20)通过将FHIT基因组克隆与间期核进行FISH检测,显示存在多个细胞群体,其FHIT等位基因的不同部分缺失。当将FISH和逆转录酶 - PCR分析获得的数据相结合时,26种细胞系中有22种显示出FHIT基因至少一个等位基因的改变。我们的数据表明,FHIT基因在HNSCC中被破坏,因此,FHIT功能的丧失可能在头颈部癌症的发生和/或进展中起重要作用。