Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: Recurrence or second primary tumor?
OBJECTIVE
In nearly all patients with glioblastoma multiforme (GBM) a local recurrence develops within a short period of time. In this paper the authors describe two patients in whom a second GBM developed after a relatively long time interval at a site remote from the primary tumor. The genetic profiles of the tumors were compared to discriminate between distant recurrence and a second primary tumor.


METHODS
Both patients harboring a supratentorial GBM were treated with surgery and local high-dose radiotherapy. Local control of the disease at the primary tumor site was achieved. Within 2 years, a second GBM developed in both patients, not only outside the previously irradiated target areas but infratentorially in one patient and in the opposite hemisphere in the other. The tumors were examined for the presence of several genetic alterations that are frequently found in GBMs--a loss of heterozygosity at chromosome regions 1p36, 10pl5, 19q13, and 22q13, and at the CDKN2A, PTEN, DMBT1, and TP53 gene regions; a TP53 mutation; and EGFR amplification. In the first patient, genetic profiling revealed that the primary tumor had an allelic imbalance for markers in several chromosome regions for which the second tumor displayed a complete loss. In the second patient, genetic profiling demonstrated the presence of genetic changes in the second tumor that were identical with and additional to those found in the primary tumor.


CONCLUSIONS
Based on the similarities between the genetic profiles of the primary and the second tumors in these patients, the authors decided that in each case the second distant GBM was a distant recurrence rather than a second independent primary tumor.
van Nifterik
Krista A
KA
Department of Radiation Oncology, Division of Radiobiology, Vrije Universiteit Medical Center, Faculty of Medicine, Amsterdam, The Netherlands. ka.vannifterik@vumc.nl
Elkhuizen
Paula H M
PH
van Andel
Rob J
RJ
Stalpers
Lukas J A
LJ
Leenstra
Sieger
S
Lafleur
M Vincent M
MV
Vandertop
W Peter
WP
Slotman
Ben J
BJ
Hulsebos
Theo J M
TJ
Sminia
Peter
P
D000328:Adult; D003937:Diagnosis, Differential; D005625:Frontal Lobe; D005909:Glioblastoma / Q000235:genetics* / Q000556:secondary* / Q000628:therapy; D006801:Humans; D015192:Infratentorial Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000235:genetics; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D013997:Time Factors