© 2012 Wichtig Editore - ISSN 0393-6155
Int J Biol Markers ( 2012; 4): e389-e394 27 -
e389
SHORT COMMUNICATION
new molecular markers for cancer detection as well as for
novel therapeutical approaches. Gene silencing by CpG
promoter methylation modulates cellular pathways by
acting directly on tumor suppressor genes and indirectly
on oncogenes through their regulators (3). The analysis
of the methylation profiles in human cancer indicates
that aberrant methylation of some of the CpG islands
are shared by multiple tumor types, whereas others are
methylated in a tumor type-specific manner (4, 5).
Hoque et al (6) reported a new set of methylated
candidate genes by using a promoter structure algorithm
and microarray data generated from 22 cancer cell lines
derived form 5 major cancer types. The newly identified
cancer-specific methylated genes were analyzed in a
panel of 300 primary tumors representing 13 types of
cancer, which included only thyroid tumors as neural
INTRODUCTION
Carcinoid tumors arise from neuroendocrine cells. They
are a heterogeneous group of neoplasms characterized by
marked different clinical behavior. Melanoma is a cancer
of the neural crest-derived cells that provide pigmentation
to skin and other tissues. Malignant cutaneous melanoma
often shows an aggressive phenotype, whereas the majority
of carcinoids have an indolent clinical course with only
a subset of the cases developing distant metastases and
resistance to treatment (1, 2).
CpG island aberrant methylation is one of the main
mechanisms for inactivation of cancer-related genes
in solid tumors. Several studies have shown that this
epigenetic modification is an early event in carcinogenesis,
representing an interesting target for the development of
Aberrant genes promoter methylation in neural crest-derived
tumors
Annamaria la Torre
1*
, Lucia Anna Muscarella
1*
, Paola Parrella
1
, Teresa Balsamo
1
, Michele Bisceglia
2
,
Vanna Maria Valori
3
, Antonella la Torre
1
, Raffaela Barbano
1
, Eleonora Perrella
4
, Maria Luana Poeta
5
,
Gennaro Melchionda
6
, Giuseppe Merla
7
, Evaristo Maiello
3
, Riccardo Pellicano
8
, Vito Michele Fazio
1,5
*Dr. Lucia Anna Muscarella and Dr. Annamaria la Torre have equally contributed to this work.
1
Laboratory of Oncology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
2
Department of Pathology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
3
Department of Oncohaematology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
4
Department of Pathology, University Campus BioMedico, Rome - Italy
5
Laboratory of Molecular Medicine and Biotechnology, Interdisciplinary Center for Biomedical Research (CIR), Univer-
sity Campus BioMedico, Rome - Italy
6
Dermatology Unit, Medical Science Department, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Ro-
tondo, Foggia - Italy
7
Medical Genetic Service, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
8
Dermatology Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
ABSTRACT
Disturbances in the epigenetic landscape by aberrant methylation of CpG islands can lead to inactivation of cancer-related
genes in solid tumors. We analyzed the promoter methylation status of 6 genes previously reported as cancer-specific meth-
ylated (MCAM, SSBP2, NISCH, B4GALT1, KIF1A and RASSF1A) in 38 neural crest-derived tumors by quantitative methyla-
tion-specific real-time PCR (QMSP). The results demonstrated that the determination of the methylation status of RASSF1A is
able to distinguish between normal and tumor samples in cutaneous melanomas, lung carcinoids and small bowel carcinoids.
MCAM methylation levels were significantly higher in lung carcinoids tumors (p=0.001), suggesting that this alteration may
represent a molecular biomarker in this tumor type.
Key words: MCAM, Methylation, Neural crest-derived tumors, RASSF1A
Received: March 14, 2012; Accepted: August 22, 2012
DOI: 10.5301/JBM.2012.9766