Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas Export

@article{citeulike:5866190, abstract = {BACKGROUND:Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60\% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas.METHODS:We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH).RESULTS:Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the NF2 tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors.CONCLUSION:Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.}, author = {Shen, Yiping and Nunes, Fabio and Rachamimov, Anat S. and James, Marianne and Mohapatra, Gayatry and Plotkin, Scott and Betensky, Rebecca and Engler, David and Roy, Jennifer and Ramesh, Vijaya and Gusella, James}, citeulike-article-id = {5866190}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1755-8794-2-42}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19589153}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19589153}, doi = {10.1186/1755-8794-2-42}, issn = {1755-8794}, journal = {BMC Medical Genomics}, keywords = {acgh, cgh, chromosomal, classification, cnv, common, instability, regions}, number = {1}, pages = {42+}, posted-at = {2009-10-01 09:26:22}, priority = {2}, title = {Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas}, url = {http://dx.doi.org/10.1186/1755-8794-2-42}, volume = {2}, year = {2009} }

TY - JOUR ID - citeulike:5866190 L3 - citeulike-article-id:5866190 N2 - BACKGROUND:Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas.METHODS:We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH).RESULTS:Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the NF2 tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors.CONCLUSION:Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members. IS - 1 JF - BMC Medical Genomics SN - 1755-8794 TI - Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas VL - 2 SP - 42 KW - acgh KW - cgh KW - chromosomal KW - classification KW - cnv KW - common KW - instability KW - regions AU - Shen, Yiping AU - Nunes, Fabio AU - Rachamimov, Anat AU - James, Marianne AU - Mohapatra, Gayatry AU - Plotkin, Scott AU - Betensky, Rebecca AU - Engler, David AU - Roy, Jennifer AU - Ramesh, Vijaya AU - Gusella, James PY - 2009/// UR - http://dx.doi.org/10.1186/1755-8794-2-42 ER -