View PDF Version - RePub - Erasmus Universiteit Rotterdam

4.7 Other tumors with loss or I'earl'angements of chromosome 22
In addition to meningiomas and vestibular schwannomas, other tumors also show non random
loss of chromosome 22. Medullary thyroid carcinoma, an endocrine tumor also found in
MEN 2, showed LOH for chromosome 22q in approximately 10% of the cases. However,
in 40% of both sporadic and familial pheochromocytomas (MEN 2), deletions of (parts of)
the long arm of chromosome 22 have been observed, with the smallest region of overlap
between D22SIO and D22S22 (Khosla et aI., 1991; Tanaka et aI., 1992). This region
includes all three putative meningioma susceptibility loci (Fig 3, Delattre et aI., 1991).
Reviewing the data on 31 ependymomas, deletions and translocations of chromosome 22 were
observed in 13 of them (Rey et aI., 1987; Bown et aI., 1988; Dal Cin and Sandberg, 1988;
Griffin et aI., 1988; Jenkins et aI., 1989; Savard and Gilchrist, 1989; James et aI., 1990;
Ranson et aI., 1992; Sainati et aI., 1992; Weremowicz et aI., 1992). One ependymal tumor
showed a der(22)t(22;?)(qI1.2;?) and another one revealed loss of one chromosome 22 and
a balanced translocation at q 13. 3 in the remaining 22 homologue (Stratton et aI., 1989;
Weremowicz et aI., 1992). This might suggest that a gene at 22q13.3 is involved. Monosomy
and structural changes of chromosome 22 are the most consistent specific chromosomal
alterations observed in malignant mesothelioma, The structural abnormalities all revealed
breakpoints at 22qll (Fletjer et aI., 1989; Hagemeijer et aI., 1990). This is in the region
where we found the MNl gene. In leiomyoma, a small tumor derived from smooth muscle
most often of the uterus, also non random loss of chromosome 22 was found (Sreekantaiah
and Sandberg, 1991). In addition, chromosome 22 deletions have been observed in gliomas
and predominate in the higher malignancy grades. LOH studies in these tumors have
identified terminal deletions due to breakpoints at 22qI3, suggesting that this region might
be the location ofa glioma suppressor gene (Rey et aI., 1993). A few reports about rhabdoid
tumors describe monosomy 22 as the only cytogenetic change in two cases and a
der(22)t(9;22(p13;qll) with a deletion of 22qter distal to BCRL2 in another (Biegel et aI.,
1990; Biegel et aI., 1992). Recently a reciprocal t(1l;22)(pI5.5;qI1.23) was identified in
such a tumor (Newsham et aI., 1994). The breakpoint was mapped proximal to the NF2
locus and might be in the region where we mapped the MNI gene. It would be very
interesting to find out if this gene is involved. LOH studies in breast cancer revealed specific
deletions of chromosome 22 sequences, with a preference in the lobular carcinomas (Devilee
38