A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer development: identification and characterization of candidate genes.
Chromosomal region 13q21-q22 harbors a putative breast cancer susceptibility gene and has been implicated as a common site for somatic deletions in a variety of malignant tumors. We have built a complete physical clone contig for a region between D13S1308 and AFM220YE9 based on 18 yeast artificial chromosome and 81 bacterial artificial chromosome (BAC) clones linked together by 22 genetic markers and 61 other sequence tagged sites. Combining data from 47 sequenced BACs (as of June 2001), we have assembled in silico an integrated 5.7-Mb genomic map with 90% sequence coverage. This area contains eight known genes, two hypothetical proteins, 24 additional Unigene clusters, and approximately 100 predicted genes and exons. We have determined the cDNA and genomic sequence, and tissue expression profiles for the KIAA1008 protein (homologous to the yeast mitotic control protein dis3+), KLF12 (AP-2 repressor), progesterone induced blocking factor 1, zinc finger transcription factor KLF5, and LIM domain only-7, and for the hypothetical proteins FLJ22624 and FLJ21869. Mutation screening of the five known genes in 19 breast cancer families has revealed numerous polymorphisms, but no deleterious mutations. These data provide a basis and resources for further analyses of this chromosomal region in the development of cancer.
Rozenblum
Ester
E
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Vahteristo
Pia
P
Sandberg
Therese
T
Bergthorsson
Jon Thor
JT
Syrjakoski
Kirsi
K
Weaver
Don
D
Haraldsson
Karin
K
Johannsdottir
Hrefna Kristin
HK
Vehmanen
Paula
P
Nigam
Savita
S
Golberger
Natalie
N
Robbins
Christiane
C
Pak
Evgenia
E
Dutra
Amalia
A
Gillander
Elizabeth
E
Stephan
Dietrich A
DA
Bailey-Wilson
Joan
J
Juo
Suh-Hang Hank
SH
Kainu
Tommi
T
Arason
Adalgeir
A
Barkardottir
Rosa Bjork
RB
Nevanlinna
Heli
H
Borg
Ake
A
Kallioniemi
Olli-P
OP
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D005387:Finland; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005819:Genetic Markers; D018398:Homeodomain Proteins; D006801:Humans; D007055:Iceland; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013548:Sweden; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D017931:DNA Primers; D018076:DNA, Complementary; D005819:Genetic Markers; D018398:Homeodomain Proteins; C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; C116184:LMO7 protein, human; D014157:Transcription Factors