Dataset Information

Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

ABSTRACT: INTRODUCTION:Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas. METHODS:We tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele. RESULTS:The 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29-1.74; P = 1.3X10(-7)) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81-1.03; P = 0.14). The associations were independent of the rs55705857 G allele. CONCLUSION:A variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology.

SUBMITTER: Rice T

PROVIDER: S-EPMC3635511 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

Rice Terri T Zheng Shichun S Decker Paul A PA Walsh Kyle M KM Bracci Paige P Xiao Yuanyuan Y McCoy Lucie S LS Smirnov Ivan I Patoka Joseph S JS Hansen Helen M HM Hsuang George G Wiemels Joe L JL Tihan Tarik T Pico Alexander R AR Prados Michael D MD Chang Susan M SM Berger Mitchel S MS Caron Alissa A Fink Stephanie S Kollmeyer Thomas T Rynearson Amanda A Voss Jesse J Kosel Matthew L ML Fridley Brooke L BL Lachance Daniel H DH Eckel-Passow Jeanette E JE Sicotte Hugues H O'Neill Brian Patrick BP Giannini Caterina C Wiencke John K JK Jenkins Robert B RB Wrensch Margaret R MR

Neuro-oncology 20130129 5

<h4>Introduction</h4>Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas.<h4> ...[more]

PMID: 23361564

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Project description:ObjectiveLGGs (low-grade gliomas) are sometimes encountered by chance during radiological examinations. These incidentally discovered LGGs (IDLGGs) were relatively under-studied in the literature. The purpose of current study is to review a cohort of patients with IDLGGs surgically treated in our institution for their clinical and histological aspects and determine their IDH1 and 1p19q status.MethodsAll patients with hemispheric LGGs receiving operation in our institution between 2001 and 2004 were reviewed. Clinical, radiological and treatment data of the patients were collected and IDLGGs were retrieved and compared with symptomatic LGGs. Histological review was carried out and formalin-fixed paraffin embedded (FFPE) tissues of IDLGGs were examined for IDH1/IDH2 mutation and 1p/19q codeletion.ResultsTwenty three IDLGGs (10.4%) were identified while 196 patients had symptomatic LGGs. The reasons for patients with IDLGGs having radiological examination included trauma (47.8%), dizziness (26.1%), unrelated headache (21.7%), and health checkup (4.4%). Clinically, patients with IDLGGs had higher preoperative KPS (P < 0.001), smaller tumor volume (P = 0.014), lower frequency of eloquent areas involvement (P < 0.001) and higher rate of complete resection (P = 0.037) comparing to those with symptomatic LGGs. Histologically, there is a preponderance of oligodendroglial differentiation with 6 oligodendrogliomas and 11 oligoastrocytomas but there were also 6 astrocytomas. IDH1 mutation and 1p/19q co-deletion were detected in 95.7% (22/23) and 69.6% (16/23) of IDLGGs, respectively. The latter encompassed all but one of the cases of oligodendroglial tumors. Patients with IDLGGs had longer overall survival than those with symptomatic LGGs (P = 0.027).ConclusionsWe conclude that the majority of IDLGGs are IDH1 mutated and are predominantly oligodendroglial tumors. With a median follow-up of 9.3 years to our series, we conclude that patients with IDLGGs had better prognosis than those with symptomatic LGGs. The favorable prognosis of IDLGGs may be accounted by the higher practicability of extensive resection, non-eloquent tumor location and smaller tumor volume. Frequent IDH1 mutation and 1p/19q co-deletion in IDLGGs may also contribute to the favorable prognosis of this subgroup of patients.

Project description:BackgroundIsocitrate dehydrogenase (IDH) mutated diffuse lower-grade gliomas (dLGG) are infiltrating brain tumors and increasing evidence is in favor of early multimodal treatment. In a Scandinavian population-based setting, we wanted to study treatment patterns over the last 15 years, focusing on the short-term postoperative course to better understand the potential negative consequences of treatment.MethodsPatients ≥ 18 years with primary IDH-mutated dLGG grade 2 and 3, operated between January 2007-June 2021 were identified. Patients were divided into subgroups (2007-2011, 2012-2016, and 2017-2021) and comparisons regarding tumor- and disease characteristics, treatment, and postoperative outcome were performed.ResultsWe identified 202 patients (n = 61, 2007-2011; n = 72, 2012-2016; n = 69, 2017-2021), where of 193 underwent resection without change in proportion of resections over time. More patients underwent complete resections in recent times (6.1%; 15.7%; 26.1%, respectively; p = 0.016). Forty-two patients had any neurological deficit postoperatively (14.8%; 23.6%; 23.2%; p = 0.379), mostly minor and transient. Differences in oncological therapy were seen between the investigated subgroups. Early radiotherapy alone (32.8%; 7%; 2.9%; p < 0.001), concomitant chemoradiotherapy (23%; 37.5%; 17.4%; p = 0.022), sequential chemoradiotherapy (0%; 18%; 49.3%; p < 0.001), and no adjuvant treatment (42.6%; 23.6%; 18.8%; p = 0.009) shifted during the studied period. Increasingly more patients received proton radiotherapy compared to photon radiotherapy during the later time periods (p < 0.001).ConclusionComplete resections were performed more often in later time periods without an apparent increase in surgical morbidity. Early adjuvant oncological treatment shifted towards providing chemotherapy and combined chemoradiotherapy more often in later time periods. Protons replaced photons as the radiation modality of choice.

Dataset Information

Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

Publications

Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology.

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