1p/19q Deletion in Gliomas, FISH, Tissue
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas are the major histologic types of human gliomas; histologic differentiation among these tumors can be difficult. Recently, it has been shown that specific genetic alterations are highly associated with specific morphologic types of gliomas.(1) In addition, specific genetic alterations seem to predict prognosis (survival), as well as response to specific chemotherapeutic and radiotherapeutic regimens, irrespective of tumor morphology.(1-4)
Deletions of the short arm of chromosome 1(1p) and long arm of chromosome 19 (19q), are strongly correlated with gliomas of oligodendroglial morphology.(5,6) Approximately 70%, 50%, and 50% of oligodendrogliomas have deletions of 19q, 1p, and of both 19q and 1p, respectively.
Combined 1p and 19q loss is infrequent in gliomas of astrocytic origin. Thus, the presence of combined 1p/19q loss is strongly suggestive that a glioma is of oligodendroglioma lineage.
Gains of chromosome 19 and of the 19 q-arm are associated with gliomas of astrocytic origin.(5)
Deletions of 1p and of both 1p and 19q also have been associated with response to various chemotherapeutic and radiotherapeutic regimens.(2,3,6) These responses have been especially associated with high-grade oligodendrogliomas (anaplastic oligodendrogliomas).
As an aid in diagnosing oligodendroglioma tumors and predicting the response of an oligodendroglioma to therapy.
The test may be useful in tumors with a complex "hybrid" morphology requiring differentiation from pure astrocytomas to support the presence of oligodendroglial differentiation/lineage.(8)
The test is indicated when a diagnosis of oligodendroglioma, both low-grade World Health Organization ([WHO], grade II) and anaplastic (WHO, grade III) is rendered. The test also is strongly recommended in mixed oligoastrocytomas.
The presence of 1p deletion and combined 1p and 19q deletion supports a diagnosis of oligodendroglioma may indicate that the patient may respond to chemotherapy and radiation therapy. The presence of gain of chromosome 19 supports a diagnosis of high-grade astrocytoma (glioblastoma multiforme). A negative result does not exclude a diagnosis of oligodendroglioma or high-grade astrocytoma.
A tumor is considered to have 1p or 19q deletion when the 1p probe to 1q probe ratio (1p/1q) or the 19q probe to 19p probe ratio (19q/19p) is <0.80. A tumor is considered to have 19q gain when the 19q/19p ratio is >1.30. A tumor is considered to have chromosome 1 or 19 gain when the percentage of nuclei with > or =3 signals is >20%. A normal 1p/1q ratio is 0.9-1.05 and a normal 19q/19 p ratio is 0.93-1.02.(7)
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 it is best used as an adjunct to existing clinical and pathologic information.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. James CD, Smith JS, Jenkins RB: Genetic and molecular basis of primary central nervous system tumors. In Cancer in the Nervous System. Edited by VA Levine. New York, Oxford University Press, 2002, pp 239-251
2. Cairncross JG, Ueki K, Zlatescu MC, et al: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998 October 7;90(19):1473-1479
3. Ino Y, Zlatescu MC, Sasaki H, et al: Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome 1p loss. J Neurosurg 2000 June;92(6):983-990
4. Smith JS, Tachibana I, Passe SM, et al: PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 2001 August 15;93(16):1246-1256
5. Smith JS, Alderete B, Minn Y, et al: Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 1999 July 15;18(28):4144-4152
6. Smith JS, Perry A, Borell TJ, et al: Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000 February;18(3):636-645
7. Jenkins RB, Curran W, Scott CB, et al: Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment group. Am J Clin Oncol 2001 October;24(5):506-508
8. Burger PC: What is an oligodendroglioma? Brain Pathol 2002;12:257-259