Localization of deletion to a 300 Kb interval of chromosome 11q13 in cervical cancer.
Previous molecular genetic studies on HeLa cell (a cervical cancer cell line) derived non-tumorigenic and tumorigenic hybrids have localized a tumor suppressor gene to the long arm of chromosome 11. Analysis of cervical cancer cell lines using chromosome 11 specific probes showed deletion and translocation of 11q13 sequences in five out of eight cell lines. Fluorescence in situ hybridization (FISH), using 11q13 specific probes, has shown interstitial deletion of 11q13 sequences in the HeLa cells. In order to determine whether 11q13 deletions occur in primary cervical tumors, we analysed 36 tumors using 20 different microsatellite and RFLP markers. Semi automated fluorescein based allelotyping was performed to identify loss of heterozygosity (LOH) in tumors. The results showed allelic loss in 17 (47%) tumors. Three different regions of loss, one near MEN1, the second near D11S913, and the third near INT2 locus were observed. The smallest region of deletion overlap at the D11S913 locus was localized to a 300 Kb distance between D11S4908 and D11S5023. Fluorescence in situ hybridization (FISH), using 11q13 specific cosmid and BAC (bacterial artificial chromosome) probes, confirmed allelic deletion in the tumors. PCR analysis further identified homozygous deletion of 11q13 sequences in a primary tumor, in HeLa cells and in two HeLa cell derived tumorigenic hybrid cell lines. The homozygous deletion in the cell lines was mapped to a 5.7 kb sequence of 11q13. We hypothesize therefore that a putative cervical cancer tumor suppressor gene exists within the 300 kb of chromosome 11q13.
Srivatsan
Eri S
ES
Department of Surgery, VAGLAHS West Los Angeles, UCLA School of Medicine, Los Angeles, California, CA 90073, USA. esrivats@ucla.edu
Chakrabarti
Rita
R
Zainabadi
Kayvan
K
Pack
Svetlana D
SD
Benyamini
Payam
P
Mendonca
Marc S
MS
Yang
Pok Kwan
PK
Kang
Kevin
K
Motamedi
Daria
D
Sawicki
Mark P
MP
Zhuang
Zhengping
Z
Jesudasan
Rachel A
RA
Bengtsson
Ulla
U
Sun
Chi
C
Roe
Bruce A
BA
Stanbridge
Eric J
EJ
Wilczynski
Sharon P
SP
Redpath
J Leslie
JL
D002503:Centromere / Q000235:genetics; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis*; D004717:Endometrium / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D019656:Loss of Heterozygosity; D008677:Metaphase; D018895:Microsatellite Repeats; D009363:Neoplasm Proteins / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins