Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung: The location of a putative tumor suppressor gene

Jonathan S. Wiest, Wilbur A. Franklin, John T. Otstot, Kristian Forbey, Marileila Varella-Garcia, Kalpana Rao, Harry Drabkin, Robert Gemmill, Steve Ahrent, David Sidransky, Geno Saccomanno, Jane W. Fountain, Marshall W. Anderson

Research output: Contribution to journalArticle

Abstract

Cytogenetic and molecular studies have implied the presence of tumor suppressor genes (TSGs) on chromosome 9p that are critical in the development of lung and other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well-defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene has been detected in approximately 30% of non-small cell lung cancer, loss of heterozygosity on 9p has been observed in greater than 70% of non-small cell lung cancers. These and other deletion mapping studies have suggested the existence of additional TSGs on 9p. This study examined chromosome 9p for TSG loci by analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers. Loss of heterozygosity was detected in all of the tumors, and homozygous deletions of the p16/CDKN2 locus were observed in 6 of the 23 tumors (26%). In addition, a novel region of homozygous deletion was detected in six tumors (26%) at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 9p control marker. Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data. The minimum region of homozygous deletion was determined by testing markers immediately proximal and distal to the D9S126 region. The data identify a homozygous loss on the short arm of chromosome 9 suggesting the presence of a novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalCancer Research
Volume57
Issue number1
StatePublished - 1997

Fingerprint

Chromosome Deletion
p16 Genes
Tumor Suppressor Genes
Squamous Cell Carcinoma
Lung
Loss of Heterozygosity
Non-Small Cell Lung Carcinoma
Neoplasms
Chromosomes
Cosmids
Chromosomes, Human, Pair 9
Cyclin-Dependent Kinases
Multiplex Polymerase Chain Reaction
Mutation Rate
Fluorescence In Situ Hybridization
Genetic Markers
Cytogenetics
Microsatellite Repeats
Lung Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wiest, J. S., Franklin, W. A., Otstot, J. T., Forbey, K., Varella-Garcia, M., Rao, K., ... Anderson, M. W. (1997). Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung: The location of a putative tumor suppressor gene. Cancer Research, 57(1), 1-6.

Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung : The location of a putative tumor suppressor gene. / Wiest, Jonathan S.; Franklin, Wilbur A.; Otstot, John T.; Forbey, Kristian; Varella-Garcia, Marileila; Rao, Kalpana; Drabkin, Harry; Gemmill, Robert; Ahrent, Steve; Sidransky, David; Saccomanno, Geno; Fountain, Jane W.; Anderson, Marshall W.

In: Cancer Research, Vol. 57, No. 1, 1997, p. 1-6.

Research output: Contribution to journalArticle

Wiest, JS, Franklin, WA, Otstot, JT, Forbey, K, Varella-Garcia, M, Rao, K, Drabkin, H, Gemmill, R, Ahrent, S, Sidransky, D, Saccomanno, G, Fountain, JW & Anderson, MW 1997, 'Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung: The location of a putative tumor suppressor gene', Cancer Research, vol. 57, no. 1, pp. 1-6.
Wiest, Jonathan S. ; Franklin, Wilbur A. ; Otstot, John T. ; Forbey, Kristian ; Varella-Garcia, Marileila ; Rao, Kalpana ; Drabkin, Harry ; Gemmill, Robert ; Ahrent, Steve ; Sidransky, David ; Saccomanno, Geno ; Fountain, Jane W. ; Anderson, Marshall W. / Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung : The location of a putative tumor suppressor gene. In: Cancer Research. 1997 ; Vol. 57, No. 1. pp. 1-6.
@article{48920854f76e44dc9d1bbccc1056e2e0,
title = "Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung: The location of a putative tumor suppressor gene",
abstract = "Cytogenetic and molecular studies have implied the presence of tumor suppressor genes (TSGs) on chromosome 9p that are critical in the development of lung and other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well-defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene has been detected in approximately 30{\%} of non-small cell lung cancer, loss of heterozygosity on 9p has been observed in greater than 70{\%} of non-small cell lung cancers. These and other deletion mapping studies have suggested the existence of additional TSGs on 9p. This study examined chromosome 9p for TSG loci by analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers. Loss of heterozygosity was detected in all of the tumors, and homozygous deletions of the p16/CDKN2 locus were observed in 6 of the 23 tumors (26{\%}). In addition, a novel region of homozygous deletion was detected in six tumors (26{\%}) at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 9p control marker. Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data. The minimum region of homozygous deletion was determined by testing markers immediately proximal and distal to the D9S126 region. The data identify a homozygous loss on the short arm of chromosome 9 suggesting the presence of a novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.",
author = "Wiest, {Jonathan S.} and Franklin, {Wilbur A.} and Otstot, {John T.} and Kristian Forbey and Marileila Varella-Garcia and Kalpana Rao and Harry Drabkin and Robert Gemmill and Steve Ahrent and David Sidransky and Geno Saccomanno and Fountain, {Jane W.} and Anderson, {Marshall W.}",
year = "1997",
language = "English (US)",
volume = "57",
pages = "1--6",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung

T2 - The location of a putative tumor suppressor gene

AU - Wiest, Jonathan S.

AU - Franklin, Wilbur A.

AU - Otstot, John T.

AU - Forbey, Kristian

AU - Varella-Garcia, Marileila

AU - Rao, Kalpana

AU - Drabkin, Harry

AU - Gemmill, Robert

AU - Ahrent, Steve

AU - Sidransky, David

AU - Saccomanno, Geno

AU - Fountain, Jane W.

AU - Anderson, Marshall W.

PY - 1997

Y1 - 1997

N2 - Cytogenetic and molecular studies have implied the presence of tumor suppressor genes (TSGs) on chromosome 9p that are critical in the development of lung and other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well-defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene has been detected in approximately 30% of non-small cell lung cancer, loss of heterozygosity on 9p has been observed in greater than 70% of non-small cell lung cancers. These and other deletion mapping studies have suggested the existence of additional TSGs on 9p. This study examined chromosome 9p for TSG loci by analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers. Loss of heterozygosity was detected in all of the tumors, and homozygous deletions of the p16/CDKN2 locus were observed in 6 of the 23 tumors (26%). In addition, a novel region of homozygous deletion was detected in six tumors (26%) at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 9p control marker. Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data. The minimum region of homozygous deletion was determined by testing markers immediately proximal and distal to the D9S126 region. The data identify a homozygous loss on the short arm of chromosome 9 suggesting the presence of a novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.

AB - Cytogenetic and molecular studies have implied the presence of tumor suppressor genes (TSGs) on chromosome 9p that are critical in the development of lung and other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well-defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene has been detected in approximately 30% of non-small cell lung cancer, loss of heterozygosity on 9p has been observed in greater than 70% of non-small cell lung cancers. These and other deletion mapping studies have suggested the existence of additional TSGs on 9p. This study examined chromosome 9p for TSG loci by analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers. Loss of heterozygosity was detected in all of the tumors, and homozygous deletions of the p16/CDKN2 locus were observed in 6 of the 23 tumors (26%). In addition, a novel region of homozygous deletion was detected in six tumors (26%) at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 9p control marker. Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data. The minimum region of homozygous deletion was determined by testing markers immediately proximal and distal to the D9S126 region. The data identify a homozygous loss on the short arm of chromosome 9 suggesting the presence of a novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.

UR - http://www.scopus.com/inward/record.url?scp=0031023126&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031023126&partnerID=8YFLogxK

M3 - Article

C2 - 8988029

AN - SCOPUS:0031023126

VL - 57

SP - 1

EP - 6

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 1

ER -