Neuroblastoma, 2p24 (MYCN) Amplification, FISH
As a prognostic factor for patients with neuroblastoma
As an aid to treatment decisions in some patients with neuroblastoma
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Neuroblastoma is a solid tumor that occurs in early childhood and is usually found in the adrenal glands, but rarely is found in other areas of the body. Approximately 25% of all neuroblastomas have amplification of the MYCN oncogene, located on chromosome 2 at p24.1. Amplification of the MYCN oncogene correlates with an unfavorable prognosis and aggressive disease.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
MYCN gene amplification is detected when the percent of cells with an abnormality exceeds the normal cutoff for the MYCN probe. A positive result is consistent with MYCN gene amplification. A negative result suggests no MYCN gene amplification. However, this result does not exclude the diagnosis of neuroblastoma.
Specimens will be considered within normal limits if they have an MYCN-to-D2Z1 ration of 1.00 to 2.00, which indicates there are an equal number of copies of the MYCN oncogene and the centromere 2. Specimens are considered amplified if they have a ratio of > or =4.00.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and is best used as an adjunct to existing clinical and pathologic information.
This test is not diagnostic for neuroblastoma. Other tumors including medulloblastoma, retinoblastoma, astrocytoma, and small cell lung cancer may have amplification of MYCN.
A blinded study using the MYCN amplification probe set was performed on 52 formalin-fixed, paraffin-embedded specimens, including 22 neuroblastoma specimens from 17 patients, 20 normal adrenal glands, and 10 Wilm's tumors. Of the 22 neuroblastoma specimens, 2 were found to be amplified and 20 were within normal limits. Fourteen of the neuroblastoma specimens were previously tested by Southern blot analysis and the 2 cases exhibiting amplification by FISH were also shown to be amplified by Southern blot. The remaining 12 specimens were found to be normal by both FISH and Southern blot. All 20 normal adrenals were found to be within normal limits. Nine of 10 Wilm's tumors were found to be within normal limits. One of the Wilm's tumors was found to be duplicated but not amplified. Duplications have a different mechanism for gaining MYCN oncogene copies and do not lead to MYCN protein overexpression.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ambros PF, Ambros IM, SIOP Europe Blastoma Pathology, Biology, and Bone Marrow Group: Pathology and biology guidelines for resectable and unresectable neuroblastic tumors and bone marrow examination guidelines. Med Pediatr Oncol 2001 Dec;37(6):492-504
2. Spitz R, Hero B, Skowron M, et al: MYCN-status in neuroblastoma: characteristics of tumours showing amplification, gain, and non-amplification. Eur J Cancer 2004 Dec;40(18):2753-2759
3. Valent A, Le Roux G, Barrois M, et al: MYCN gene overrepresentation detected in primary neuroblastoma tumour cells without amplification. J Pathol 2002 Dec;198(4):495-501
4. Schwab M: Amplified MYCN in human neuroblastoma: paradigm for the translation of molecular genetics to clinical oncology. Ann NY Acad Sci 2002 Jun;963:63-73