TY - JOUR
T1 - Definition of a Region of Loss of Heterozygosity at Chromosome 11q23.3-25 in Head and Neck Squamous Cell Carcinoma Using Laser Capture Microdissection Technique
AU - Tan, Dongfeng
AU - Wiseman, Sam
AU - Zhou, Youtai
AU - Li, Qiang
AU - Ward, Pamela
AU - Slocum, Harry K.
AU - Alrawi, Sadir
AU - Loree, Thom
AU - Hicks, Wesley
AU - Rigual, Nestor
AU - Anderson, Garth
AU - Stoler, Daniel
PY - 2004/3
Y1 - 2004/3
N2 - To date, loss of heterozygosity (LOH) studies on HNSCC have had limited success in identifying a confined region of loss on chromosome 11q partially due to the heterogeneous nature of tumor tissue examined. Additionally, little is known about the role of the 11q allelic deletion in HNSCC tumorigenesis and current reports are conflicting. The aim of this study was to better define LOH at distal 11q by using combination of a pure cell population procured by laser capture microdissection (LCM) and subsequent sensitive PCR amplification of polymorphic microsatellites. This study analyzed HNSCC for LOH using a panel of 5 microsatellite markers spanning 11q23-25. Thirty-four paired DNA samples from tumor and autologous normal tissue were harvested by LCM technique to ensure a pure cell population for PCR amplification. Approximately 2000 to 3000 cells were procured from each sample. Twenty-one of 34 cases(62%, P < 0.001) showed LOH on at least one of the loci examined. The highest frequency of LOH was found at the 11q23.3-25 segment, with 44% at marker D11S968 and 35% at marker D11S1316. A distinct novel region of frequent LOH at 11q23.3-25, defined by D11S1316 and D11S968, was identified. No allelic loss was found in any normal squamous tissue samples. To study LOH in HNSCC, combination of pure cell population procurement by LCM and sensitive PCR provides a more accurate approach than the conventional method using a bulk of heterogeneous tissue. A novel region of LOH at 11q23.3-25 was defined. LOH in this region may harbor putative tumor suppressor gene(s) critical for HNSCC. Furthermore, these allelic losses were not found in any non-neoplastic squamous tissue samples, clarifying prior discrepant data.
AB - To date, loss of heterozygosity (LOH) studies on HNSCC have had limited success in identifying a confined region of loss on chromosome 11q partially due to the heterogeneous nature of tumor tissue examined. Additionally, little is known about the role of the 11q allelic deletion in HNSCC tumorigenesis and current reports are conflicting. The aim of this study was to better define LOH at distal 11q by using combination of a pure cell population procured by laser capture microdissection (LCM) and subsequent sensitive PCR amplification of polymorphic microsatellites. This study analyzed HNSCC for LOH using a panel of 5 microsatellite markers spanning 11q23-25. Thirty-four paired DNA samples from tumor and autologous normal tissue were harvested by LCM technique to ensure a pure cell population for PCR amplification. Approximately 2000 to 3000 cells were procured from each sample. Twenty-one of 34 cases(62%, P < 0.001) showed LOH on at least one of the loci examined. The highest frequency of LOH was found at the 11q23.3-25 segment, with 44% at marker D11S968 and 35% at marker D11S1316. A distinct novel region of frequent LOH at 11q23.3-25, defined by D11S1316 and D11S968, was identified. No allelic loss was found in any normal squamous tissue samples. To study LOH in HNSCC, combination of pure cell population procurement by LCM and sensitive PCR provides a more accurate approach than the conventional method using a bulk of heterogeneous tissue. A novel region of LOH at 11q23.3-25 was defined. LOH in this region may harbor putative tumor suppressor gene(s) critical for HNSCC. Furthermore, these allelic losses were not found in any non-neoplastic squamous tissue samples, clarifying prior discrepant data.
KW - Chromosome 11
KW - Head and neck cancer
KW - Laser microdissection
KW - Loss of heterozygosity
UR - http://www.scopus.com/inward/record.url?scp=10744223331&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744223331&partnerID=8YFLogxK
U2 - 10.1097/00019606-200403000-00006
DO - 10.1097/00019606-200403000-00006
M3 - Article
C2 - 15163007
AN - SCOPUS:10744223331
SN - 1052-9551
VL - 13
SP - 33
EP - 40
JO - Diagnostic Molecular Pathology
JF - Diagnostic Molecular Pathology
IS - 1
ER -