Subclassification of nerve sheath tumors by gene expression profiling

TY - JOUR

T1 - Subclassification of nerve sheath tumors by gene expression profiling

AU - Holtkamp, Nikola

AU - Reuss, David E

AU - Atallah, Isis

AU - Kuban, Ralf-Jürgen

AU - Hartmann, Christian

AU - Mautner, Victor-F

AU - Frahm, Silke

AU - Friedrich, Reinhard E

AU - Algermissen, Bernd

AU - Pham, Van-Anh

AU - Prietz, Sandra

AU - Rosenbaum, Thorsten

AU - Estevez-Schwarz, Lope

AU - von Deimling, Andreas

PY - 2004/7/1

Y1 - 2004/7/1

N2 - Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas plexiform neurofibromas are only observed in one-third of the patients. NF1-patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1-patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1-associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.

AB - Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas plexiform neurofibromas are only observed in one-third of the patients. NF1-patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1-patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1-associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.

KW - Adolescent

KW - Adult

KW - Aged

KW - Cell Line, Tumor

KW - Gene Expression

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Image Processing, Computer-Assisted

KW - In Situ Hybridization

KW - Middle Aged

KW - Nerve Sheath Neoplasms

KW - Neurofibroma

KW - Neurofibroma, Plexiform

KW - Neurofibromatosis 1

KW - Oligonucleotide Array Sequence Analysis

M3 - SCORING: Journal article

C2 - 15446580

VL - 14

SP - 258

EP - 264

JO - BRAIN PATHOL

JF - BRAIN PATHOL

SN - 1015-6305

IS - 3

ER -