*6.1.1. Mechanism of the combined loss of the chromosomes 1p and 19q*

**5. Treatment and prognosis**

344 Neurooncology - Newer Developments

**6.1. 1p/19q chromosomal status**

tumors [22, 24].

mas or OAs [27].

OAs responded less favourably to chemotherapy (CHT) due to the chemoresistance of their astrocytic components [25]. Studies have shown that the standard of care for 1p/19q co-deleted oligodendroglial tumors should be the combination of CHT and radiotherapy (RT). In OA, a favourable prognosis was associated to young age, grade II and extent of resection [26].

Compared to astrocytomas, OAs shared with oligodendrogliomas a more favourable prog‐ nosis and an improved response to adjuvant therapy. The NOA-04 prospective trial on anaplastic gliomas reported virtually identical outcomes for patients with oligodendroglio‐

**6. New criteria for glioma diagnosis after the "ISN-Haarlem Consensus"**

Our knowledge on the nature of OA underwent a profound change after the "International Society of Neuropathology (ISN)-Haarlem *Consensus*" guidelines led to the official recogni‐ tion of the indispensability of the genetic analysis in order to obtain an "integrated" diagno‐ sis of gliomas [28]. Referred to grade II and III adult gliomas, this new approach would involve a combination of histologic and molecular data based on the 1p/19q, isocitrate dehydrogen‐ ase (IDH) 1/2 and α-thalassemia/mental retardation syndrome X-linked (ATRX) status.

The genetic hallmark of oligodendroglial tumors is a combined chromosomal deletion of the short arm of the chromosome 1 (1p) and the long arm of the chromosome 19 (19q). Com‐ bined 1p and 19q losses were described in 80–90% of grade II and in 50–70% of grade III

The 1p/19q chromosomal status was recognized as an important diagnostic biomarker in the clinical practice. The 1p/19q co-deletion was reported in 60–70% of oligodendrogliomas with a classical histologic phenotype (perinuclear "halo" and "chicken wire" vascular pattern). Partial 1p or 19q deletion occurred in approximately 75% of the cases [29, 30]. Oligodendro‐ glial tumors with 1p/19q co-deletion were observed to typically arise at an extra-temporal location, whereas tumors with intact 1p/19q at the temporal lobe [22]. In contrast, childhood

Importantly, the occurrence of 1p/19q co-deletion supports the diagnosis of oligodendroglio‐ ma, especially when histology is atypical. However, its absence does not exclude this diagno‐

In OA, the frequency of the 1p/19q co-deletion was approximately 50% [22]. Virtually, it was mutually exclusive with LOH of chromosome 17p13 and TP53 mutations, both typical of astrocytic tumors. In OA, the 1p/19q co-deletion was referred to the oligodendroglial compo‐

oligodendrogliomas only rarely exhibited chromosomal abnormalities.

nent, whereas TP53 mutations to the astrocytic one.

sis, leaving unsolved the question of oligodendrogliomas with intact 1p/19q.

The mechanism of the combined loss of the two chromosomal arms is an unbalanced t(1;19) (q10;p10) translocation of 19p to 1q. A centromeric or pericentromeric translocation of chromosomes 1 and 19 results in two derivative chromosomes, der(1;19)(p10;q10) and der(1;19)(q10;p10), followed by the loss of the derivative chromosome containing the short arm of chromosome 1 and the long arm of chromosome 19 [31, 32].

The extent of the 1p/19q co-deletion has important diagnostic and prognostic implications. The chromosomal arm 1p is entirely deleted only in pure oligodendroglial tumors and the wholearm 1p deletion has a strong favorable prognostic significance. Small telomeric (1p36) or interstitial 1p deletions are frequent as well, but with an opposite prognostic significance; they associate neither withdeletion on the chromosomal arm 19q [33] nor with response to CHT [34].

While the total 1p/19q co-deletion is almost completely exclusive of oligodendrogliomas, partial 1p deletions are frequent in GBMs and isolated 19q loss in mixed and astrocytic gliomas in relation to the malignant transformation [35, 36].

Currently, there is a general agreement to diagnose the classical oligodendroglioma only in presence of a whole-arm 1p/19q co-deletion [37, 38].

Most oligodendrogliomas with 1p/19q co-deletion harbor IDH1/2, telomerase reverse transcriptase (TERT), homolog of the *Drosophila capicua* (CIC) and far upstream elementbinding protein 1 (FUBP1) somatic mutations, and O6 -methylguanine-DNA methyltransfer‐ ase (MGMT) or CDKN2A (p14ARF) promoter hypermethylation [37, 39–41].
