Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

Amy E. Rose, Laura Poliseno, Jinhua Wang, Michael Clark, Alexander Pearlman, Guimin Wang, Eleazar C. Vega Y Saenz De Miera, Ratna Medicherla, Paul J. Christos, Richard Shapiro, Anna Pavlick, Farbod Darvishian, Jiri Zavadil, David Polsky, Eva Hernando, Harry Ostrer, Iman Osman

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.

Original languageEnglish (US)
Pages (from-to)2561-2571
Number of pages11
JournalCancer Research
Volume71
Issue number7
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Fingerprint

Genomics
Linear Models
Melanoma
Aldehyde Dehydrogenase
Genes
Gene Expression
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rose, A. E., Poliseno, L., Wang, J., Clark, M., Pearlman, A., Wang, G., ... Osman, I. (2011). Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression. Cancer Research, 71(7), 2561-2571. https://doi.org/10.1158/0008-5472.CAN-10-2958

Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression. / Rose, Amy E.; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega Y Saenz De Miera, Eleazar C.; Medicherla, Ratna; Christos, Paul J.; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman.

In: Cancer Research, Vol. 71, No. 7, 01.04.2011, p. 2561-2571.

Research output: Contribution to journalArticle

Rose, AE, Poliseno, L, Wang, J, Clark, M, Pearlman, A, Wang, G, Vega Y Saenz De Miera, EC, Medicherla, R, Christos, PJ, Shapiro, R, Pavlick, A, Darvishian, F, Zavadil, J, Polsky, D, Hernando, E, Ostrer, H & Osman, I 2011, 'Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression', Cancer Research, vol. 71, no. 7, pp. 2561-2571. https://doi.org/10.1158/0008-5472.CAN-10-2958
Rose, Amy E. ; Poliseno, Laura ; Wang, Jinhua ; Clark, Michael ; Pearlman, Alexander ; Wang, Guimin ; Vega Y Saenz De Miera, Eleazar C. ; Medicherla, Ratna ; Christos, Paul J. ; Shapiro, Richard ; Pavlick, Anna ; Darvishian, Farbod ; Zavadil, Jiri ; Polsky, David ; Hernando, Eva ; Ostrer, Harry ; Osman, Iman. / Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression. In: Cancer Research. 2011 ; Vol. 71, No. 7. pp. 2561-2571.
@article{5d56b2995e6d43bf87ce1d9340666797,
title = "Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression",
abstract = "Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.",
author = "Rose, {Amy E.} and Laura Poliseno and Jinhua Wang and Michael Clark and Alexander Pearlman and Guimin Wang and {Vega Y Saenz De Miera}, {Eleazar C.} and Ratna Medicherla and Christos, {Paul J.} and Richard Shapiro and Anna Pavlick and Farbod Darvishian and Jiri Zavadil and David Polsky and Eva Hernando and Harry Ostrer and Iman Osman",
year = "2011",
month = "4",
day = "1",
doi = "10.1158/0008-5472.CAN-10-2958",
language = "English (US)",
volume = "71",
pages = "2561--2571",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

AU - Rose, Amy E.

AU - Poliseno, Laura

AU - Wang, Jinhua

AU - Clark, Michael

AU - Pearlman, Alexander

AU - Wang, Guimin

AU - Vega Y Saenz De Miera, Eleazar C.

AU - Medicherla, Ratna

AU - Christos, Paul J.

AU - Shapiro, Richard

AU - Pavlick, Anna

AU - Darvishian, Farbod

AU - Zavadil, Jiri

AU - Polsky, David

AU - Hernando, Eva

AU - Ostrer, Harry

AU - Osman, Iman

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.

AB - Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.

UR - http://www.scopus.com/inward/record.url?scp=79953318394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953318394&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-2958

DO - 10.1158/0008-5472.CAN-10-2958

M3 - Article

C2 - 21343389

AN - SCOPUS:79953318394

VL - 71

SP - 2561

EP - 2571

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 7

ER -