Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p

Jaume Mora, Nai Kong V. Cheung, Brian H. Kushner, Michael P. LaQuaglia, Kim Kramer, Melissa Fazzari, Glenn Heller, Lishi Chen, William L. Gerald

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semiautomated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55%) and at 1p22 (56%). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42%). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalJournal of Molecular Diagnostics
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Loss of Heterozygosity
Neuroblastoma
Chromosomes
Ganglioneuroma
Polyploidy
Chromosomes, Human, Pair 1
Neoplasms
Diploidy
DNA
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p. / Mora, Jaume; Cheung, Nai Kong V.; Kushner, Brian H.; LaQuaglia, Michael P.; Kramer, Kim; Fazzari, Melissa; Heller, Glenn; Chen, Lishi; Gerald, William L.

In: Journal of Molecular Diagnostics, Vol. 2, No. 1, 01.01.2000, p. 37-46.

Research output: Contribution to journalArticle

Mora, Jaume ; Cheung, Nai Kong V. ; Kushner, Brian H. ; LaQuaglia, Michael P. ; Kramer, Kim ; Fazzari, Melissa ; Heller, Glenn ; Chen, Lishi ; Gerald, William L. / Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p. In: Journal of Molecular Diagnostics. 2000 ; Vol. 2, No. 1. pp. 37-46.
@article{aaacf6f5b7be4d368165756a21190bdc,
title = "Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p",
abstract = "Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semiautomated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55{\%}) and at 1p22 (56{\%}). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42{\%}). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.",
author = "Jaume Mora and Cheung, {Nai Kong V.} and Kushner, {Brian H.} and LaQuaglia, {Michael P.} and Kim Kramer and Melissa Fazzari and Glenn Heller and Lishi Chen and Gerald, {William L.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1016/S1525-1578(10)60613-7",
language = "English (US)",
volume = "2",
pages = "37--46",
journal = "Journal of Molecular Diagnostics",
issn = "1525-1578",
publisher = "Association of Molecular Pathology",
number = "1",

}

TY - JOUR

T1 - Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p

AU - Mora, Jaume

AU - Cheung, Nai Kong V.

AU - Kushner, Brian H.

AU - LaQuaglia, Michael P.

AU - Kramer, Kim

AU - Fazzari, Melissa

AU - Heller, Glenn

AU - Chen, Lishi

AU - Gerald, William L.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semiautomated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55%) and at 1p22 (56%). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42%). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.

AB - Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semiautomated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55%) and at 1p22 (56%). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42%). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.

UR - http://www.scopus.com/inward/record.url?scp=0034139858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034139858&partnerID=8YFLogxK

U2 - 10.1016/S1525-1578(10)60613-7

DO - 10.1016/S1525-1578(10)60613-7

M3 - Article

C2 - 11272900

AN - SCOPUS:0034139858

VL - 2

SP - 37

EP - 46

JO - Journal of Molecular Diagnostics

JF - Journal of Molecular Diagnostics

SN - 1525-1578

IS - 1

ER -