Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants

Jennifer B. Sherwood, Narayan Shivapurkar, W. Michael Lin, Raheela Ashfaq, David S. Miller, Adi F. Gazdar, Carolyn Y. Muller

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objective. Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different 'hotspot' targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. Methods. Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. Results. Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. Conclusions. Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalGynecologic Oncology
Volume79
Issue number1
DOIs
StatePublished - 2000

Fingerprint

Squamous Cell Neoplasms
Chromosome Deletion
Chromosomes, Human, Pair 4
Uterine Cervical Neoplasms
Loss of Heterozygosity
Adenocarcinoma
Human papillomavirus 18
Gene-Environment Interaction
Human papillomavirus 16
Neoplasms
Carcinoma
Polymerase Chain Reaction
Histology
Chromosomes
Lung
DNA
Genes

Keywords

  • Adenocarcinoma
  • Allele loss
  • Human papillomavirus
  • Loss of heterozygosity
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants. / Sherwood, Jennifer B.; Shivapurkar, Narayan; Lin, W. Michael; Ashfaq, Raheela; Miller, David S.; Gazdar, Adi F.; Muller, Carolyn Y.

In: Gynecologic Oncology, Vol. 79, No. 1, 2000, p. 90-96.

Research output: Contribution to journalArticle

Sherwood, Jennifer B. ; Shivapurkar, Narayan ; Lin, W. Michael ; Ashfaq, Raheela ; Miller, David S. ; Gazdar, Adi F. ; Muller, Carolyn Y. / Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants. In: Gynecologic Oncology. 2000 ; Vol. 79, No. 1. pp. 90-96.
@article{cb392eb984364467a849408383e0fbe4,
title = "Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants",
abstract = "Objective. Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different 'hotspot' targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. Methods. Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. Results. Loss at any chromosome 4 locus occurred in 92{\%} of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76{\%} (R1, 4q34-q35), 48{\%} (R2, 4q25-q26), 36{\%} (R3, 4p15.1-p15.3), and 26{\%} (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83{\%}) and in AC at 4p (4p15.3; 50{\%}). Overall LOH on the p arm was significant in AC (82{\%}) compared to SCCA (31{\%}) (P = 0.02). HPV detection was similar in SCCA (85{\%}) and AC (73{\%}), and HPV 16/18 subtypes were similarly represented in both histologies. Conclusions. Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes. (C) 2000 Academic Press.",
keywords = "Adenocarcinoma, Allele loss, Human papillomavirus, Loss of heterozygosity, Squamous cell carcinoma",
author = "Sherwood, {Jennifer B.} and Narayan Shivapurkar and Lin, {W. Michael} and Raheela Ashfaq and Miller, {David S.} and Gazdar, {Adi F.} and Muller, {Carolyn Y.}",
year = "2000",
doi = "10.1006/gyno.2000.5922",
language = "English (US)",
volume = "79",
pages = "90--96",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants

AU - Sherwood, Jennifer B.

AU - Shivapurkar, Narayan

AU - Lin, W. Michael

AU - Ashfaq, Raheela

AU - Miller, David S.

AU - Gazdar, Adi F.

AU - Muller, Carolyn Y.

PY - 2000

Y1 - 2000

N2 - Objective. Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different 'hotspot' targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. Methods. Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. Results. Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. Conclusions. Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes. (C) 2000 Academic Press.

AB - Objective. Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different 'hotspot' targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. Methods. Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. Results. Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. Conclusions. Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes. (C) 2000 Academic Press.

KW - Adenocarcinoma

KW - Allele loss

KW - Human papillomavirus

KW - Loss of heterozygosity

KW - Squamous cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=0033778056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033778056&partnerID=8YFLogxK

U2 - 10.1006/gyno.2000.5922

DO - 10.1006/gyno.2000.5922

M3 - Article

VL - 79

SP - 90

EP - 96

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 1

ER -