A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus

Abstract

Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that theMEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM andD11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations.[The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236,AF001540–AF001547, AF001433–AF001436, AF001891–AF001893,N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.]

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

“…Examination of the chromosome 11 sequence revealed perfect homology with a previously identified gene, Alpha (29,30), which is fused to the first intron of TFEB (Fig. 4A).…”

“…The Alpha gene is on chromosome 11 (29,30) and produces a 7.5-to 8.5-kb intronless transcript (GenBank accession number AP000769.4). The region of Alpha sequenced in the TFEB fusion corresponds to nucleotides 733-1580 (GenBank accession number AF203815).…”

“…TFEB has not previously been implicated in malignancy. The Alpha gene resides near the multiple endocrine neoplasia type 1 locus (29,36) in a region implicated in chromosomal abnormalities of various other tumors (36). The Alpha gene is unusual in that it is very AT-rich, transcribed in an intronless fashion, and contains no ORF of significant length.…”

MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer

“…Database searches revealed that this sequence has been described as part of different ESTs. Two separate ESTs were mapped to chromosome 11q13 in a radiation hybrid map (James et al, 1994) and later identified to belong to a single transcript of 8.5 kb (Guru et al, 1997), preliminarily named a gene (GenBank Acc AF203815). This transcript was isolated again in searches for translocation breakpoints at 11q13 (van Asseldonk et al, 2000).…”

Paraspeckles as rhythmic nuclear mRNA anchorages responsible for circadian gene expression

“…[23][24][25][26] While a short and a long transcript previously identified as MENe (Neat1-1) and MENb (Neat1-2), respectively. 25,27 are generated from the same promoter, Neat1-1 alone cannot induce paraspeckle formation since specific depletion of Neat1-2 leads to disruption of paraspeckles. 25 While paraspeckles detected by RNA FISH of Neat1 appeared as round foci when visualized under a confocal microscope, we showed that they appeared more likely as oblong structures with smaller dimensions after use of a combination of Neat1 RNA FISH and Super Resolution STORM analysis (as designed in Fig.…”