Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc

Kelly G. Paulson, Bianca D. Lemos, Bin Feng, Natalia Jaimes, Pablo F. Pẽas, Xiaohui Bi, Elizabeth Maher, Lisa Cohen, J. Helen Leonard, Scott R. Granter, Lynda Chin, Paul Nghiem

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

Original languageEnglish (US)
Pages (from-to)1547-1555
Number of pages9
JournalJournal of Investigative Dermatology
Volume129
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Merkel Cell Carcinoma
Amplification
Tumors
Cells
Neoplasms
Chromosomes
Merkel cell polyomavirus
Skin
Chromosomes, Human, Pair 4
myc Genes
Comparative Genomic Hybridization
Chromosomes, Human, Pair 1
DNA
Small Cell Lung Carcinoma
Skin Neoplasms
Oligonucleotide Array Sequence Analysis
Microarrays
Aberrations
Oligonucleotides
RNA

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Paulson, K. G., Lemos, B. D., Feng, B., Jaimes, N., Pẽas, P. F., Bi, X., ... Nghiem, P. (2009). Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc. Journal of Investigative Dermatology, 129(6), 1547-1555. https://doi.org/10.1038/jid.2008.365

Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc. / Paulson, Kelly G.; Lemos, Bianca D.; Feng, Bin; Jaimes, Natalia; Pẽas, Pablo F.; Bi, Xiaohui; Maher, Elizabeth; Cohen, Lisa; Leonard, J. Helen; Granter, Scott R.; Chin, Lynda; Nghiem, Paul.

In: Journal of Investigative Dermatology, Vol. 129, No. 6, 06.2009, p. 1547-1555.

Research output: Contribution to journalArticle

Paulson, KG, Lemos, BD, Feng, B, Jaimes, N, Pẽas, PF, Bi, X, Maher, E, Cohen, L, Leonard, JH, Granter, SR, Chin, L & Nghiem, P 2009, 'Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc', Journal of Investigative Dermatology, vol. 129, no. 6, pp. 1547-1555. https://doi.org/10.1038/jid.2008.365
Paulson, Kelly G. ; Lemos, Bianca D. ; Feng, Bin ; Jaimes, Natalia ; Pẽas, Pablo F. ; Bi, Xiaohui ; Maher, Elizabeth ; Cohen, Lisa ; Leonard, J. Helen ; Granter, Scott R. ; Chin, Lynda ; Nghiem, Paul. / Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 6. pp. 1547-1555.
@article{08f86c49be7b476989451b88691c4da1,
title = "Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc",
abstract = "Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.",
author = "Paulson, {Kelly G.} and Lemos, {Bianca D.} and Bin Feng and Natalia Jaimes and Pẽas, {Pablo F.} and Xiaohui Bi and Elizabeth Maher and Lisa Cohen and Leonard, {J. Helen} and Granter, {Scott R.} and Lynda Chin and Paul Nghiem",
year = "2009",
month = "6",
doi = "10.1038/jid.2008.365",
language = "English (US)",
volume = "129",
pages = "1547--1555",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc

AU - Paulson, Kelly G.

AU - Lemos, Bianca D.

AU - Feng, Bin

AU - Jaimes, Natalia

AU - Pẽas, Pablo F.

AU - Bi, Xiaohui

AU - Maher, Elizabeth

AU - Cohen, Lisa

AU - Leonard, J. Helen

AU - Granter, Scott R.

AU - Chin, Lynda

AU - Nghiem, Paul

PY - 2009/6

Y1 - 2009/6

N2 - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

AB - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

UR - http://www.scopus.com/inward/record.url?scp=67349267297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349267297&partnerID=8YFLogxK

U2 - 10.1038/jid.2008.365

DO - 10.1038/jid.2008.365

M3 - Article

C2 - 19020549

AN - SCOPUS:67349267297

VL - 129

SP - 1547

EP - 1555

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 6

ER -