Parental origin of chromosome 22 loss in sporadic and NF2 neuromas

Fontaine, Bertrand; Sanson, Marc; Delattre, Olivier; Menon, Anil G.; Rouleau, Guy A.; Seizinger, Bernd R.; Jewell, Ann; Hanson, Mark P.; Aurias, Alain; Martuza, Robert L.; Gusella, James F.; Thomas, Gilles

doi:10.1016/0888-7543(91)90513-e

Cited by 21 publications

(10 citation statements)

References 19 publications

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“…This effect should also be apparent if sporadically occurring tumors are examined. Previous studies have found loss of both maternal and paternal chromosome 22 in sporadic schwannomas [22] and meningiomas [48]. These studies of sporadic tumors did show an unexplained tendency towards maternal allele loss (21 of 32 tumors examined, 66%) that was only slightly less than our findings in NF2-associated tumors.…”

Section: Discussioncontrasting

confidence: 82%

“…Because the "two-hit" model predicts that the allele lost in tumor formation is the normal allele, the allele retained may then be inferred to be that carrying the constitutional mutation. Only one previous study has addressed the question of parental origin of new mutations in NF2 patients [22]. Utilizing restriction fragment length polymorphism (RFLP) markers in NF2-related tumors, the authors found paternal origin of new mutations in six of eight sporadic NF2 patients.…”

Section: Introductionmentioning

confidence: 99%

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The parental origin of new mutations in neurofibromatosis 2

Mautner¹,

Parry

Jacoby

et al. 2000

neurogenetics

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Neurofibromatosis 2 (NF2) is an autosomal dominant disorder characterized by schwannomas and meningiomas that develop after inactivation of both copies of the NF2 gene. Approximately half of all patients with NF2 have unaffected parents and the disease results from new mutations at the NF2 locus. Loss of heterozygosity (LOH) in tumor specimens due to deletions covering the normal NF2 allele can be used to infer the haplotypes surrounding underlying mutations and determine the allelic origin of new mutations. We studied 71 sporadic NF2 patients using both LOH and pedigree analysis and compared the parental origin of the new mutation with the underlying molecular change. In the 45 informative individuals, 31 mutations (69%) were of paternal and 14 (31%) were of maternal origin (P=0.016). Comparison with corresponding constitutional mutations revealed no correlation between parental origin and the type or location of the mutations. However, in 4 of 6 patients with somatic mosaicism the NF2 mutation was of maternal origin. A slight parent of origin effect on severity of disease was found. Further clinical and molecular studies are needed to determine the basis of these unexpected observations.

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Section: Discussioncontrasting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

The parental origin of new mutations in neurofibromatosis 2

Mautner¹,

Parry

Jacoby

et al. 2000

neurogenetics

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“…In our series of acoustic schwannomas, we found loss of heterozygosity for chromosome 22 markers in 22% of the tumors. This figure is considerably lower than estimated previously (about 40%; Seizinger et al, 1986;Fontaine et al, 1991b). On the other hand, Jacoby et al (1990) failed to find chromosome 22 loss in their series of seven informative schwannomas.…”

Section: Discussioncontrasting

confidence: 53%

“…Molecular analysis of bilateral acoustic schwannomas of NF2 patients and unilateral acoustic schwannomas of sporadic cases revealed specific loss of chromosome 22, suggesting that the NF2 gene is a tumor suppressor gene of which both alleles are inactivated in the tumor. Complete loss of one copy of chromosome 22 has frequently been found in acoustic schwannomas (Seizinger et al, 1986(Seizinger et al, , 1987bCouturier et al, 1990;Fontaine et al, 1991b). However, deletion of part of chromosome 22 has only been described for two acoustic schwannomas (Seizinger et al, 1987b).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of chromosome 22 deletions in schwannomas

Brouwer-Mladin

et al. 1992

Genes Chromosomes & Cancer

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Schwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that originate from Schwann cells. Acoustic neurinomas are the most frequent cranial schwannomas. They might develop sporadically or in the context of neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is frequently found in acoustic schwannomas, suggesting that the NF2 gene is a tumor suppressor gene involved in the genesis of these tumors. Only a few spinal schwannomas have been molecularly characterized so far, showing that chromosome 22 loss might also occur in these tumors. Here we present the molecular analysis of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other locations (including other cranial nerves and spinal and peripheral nerves). Most of these tumors were from sporadic cases. Multiple schwannomas of various locations were analyzed in two patients with NF2. We found partial or complete monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non-acoustic schwannomas. The tumors with partial monosomy included four with terminal deletions and one with a deletion of the centromeric part of the long arm of chromosome 22. The region between the beta B2-1 crystallin locus (CRYB2A) and the myoglobin locus (MB) was commonly deleted in these tumors. Our studies suggest that a schwannoma-related tumor suppressor gene within this region, which might be the NF2 gene, is involved in the development of schwannomas of various locations in the nervous system. Our studies indicate that the second hit in the genesis of different schwannomas within one (predisposed) NF2 patient occurs independently and via different mechanisms.

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“…NF‐2‐associated VS tend to present at a younger age 1 and are of a larger size at clinical presentation than their sporadic counterparts 9 . A maternal effect, which is defined as the earlier presentation and more rapid progression of VS in maternally‐inherited cases, has also been noted to occur in NF‐2 10 . Histologically, VS in NF‐2 have foci of higher cellularity and more lobular growth patterns as compared with their sporadic counterparts 11 .…”

Section: Discussionmentioning

confidence: 99%

Familial Occurrence of Unilateral Vestibular Schwannoma

et al. 1997

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Vestibular schwannoma (VS) may present clinically in one of two forms: sporadic unilateral or hereditary bilateral. Almost all cases of familial transmission have been associated with the diagnosis of neurofibromatosis type II (NF-2). In this report, we describe nine families (18 individuals) presenting with unilateral VS without evidence of NF-2. In four of the nine families, the affected individuals were of parent-offspring relationship, in three families they were cousin-cousin, and in the remaining two families, they were sibling-sibling and aunt-nephew. No other members of the families were diagnosed with NF-2. There was no evidence for gender predilection or genomic imprinting among affected individuals. This study suggests that familial occurrence of unilateral VS may be genetically inherited as it occurs more commonly than would be estimated by chance alone. Future genetic studies will elucidate whether occurrence of unilateral VS in these families represents a variable expression of NF-2, chance occurrence of unilateral VS in families, or a new genetic disorder.

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Parental origin of chromosome 22 loss in sporadic and NF2 neuromas

Cited by 21 publications

References 19 publications

The parental origin of new mutations in neurofibromatosis 2

The parental origin of new mutations in neurofibromatosis 2

Molecular characterization of chromosome 22 deletions in schwannomas

Familial Occurrence of Unilateral Vestibular Schwannoma

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