Etchevers:Notebook/Genomics of hNCC/2008/12/10

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R.I.P. and NB

Finally threw away the last remnants of the cells that had been in Rich and Neural medium. There were still cells left in the "neural" culture but they were pretty much pericyte-like and those can hang on for months. The medium had evaporated, meanwhile (after 10 days!).

When I was last in Paris I had established 2x C13 new hNCC cultures that Sophie says are growing well.

  • Heather 02:54, 10 December 2008 (EST):

Looking at neuroblastoma data. In particular, cf. the paper by Chen et al. published at the same time as Janoueix-Lerosey et al. on the CNVs that were identified in NB cell lines.

  • Using UCSC, copying all the gene names and full definitions when available for those in CNV intervals not corresponding to MYCN (the majority) or to ALK (the subject of these papers, at 2p23).
  • I note that although much does correspond, they left some genes out and included some that were near but not precisely in the intervals in the Supplementary Table 4. I have decided to do the same and see which genes are near intervals, especially when there are large gene deserts.
  • Then will ask Sophie to see if any of the NB lines or tumors are over-expressing any of these genes relative to the NCC. It will have to be one by one or few by few because the NB population is highly heterogeneous. Any of the high MYC ones should be set aside, as for the ALK mutated ones (8/24 lines eg NB-1, 13/215 fresh tumors for Chen et al and (26+135)/592 cases on CGH array for Janoueix et al. - make sure to remove CLB-GA,CLB-GE and CLB-BAR and KCNR lines!).

When I've made the table, will put up on GoogleDocs.

  • In this paper from EMBO J, where Mycn was overexpressed under the TH promoter in mice which subsequently developed NB's, an ensuing effect they noted by CGH array was a gain or loss of chromosomal material:

"Thirteen tumors (all from hemizygous mice) showed gains and losses of chromosomal regions (Figure 8, Table II). In mice hemizygous for the MYCN transgene, chromosomal regions were most commonly gained on chromosomes 11 (5/16) and 17 (6/16). These regions are syntenic with human chromosomes 6 and 17 respectively (Copeland et al., 1993), both of which commonly are gained in human neuroblastoma (Plantaz et al., 1997). Chromosomal loss was most often detected on chromosomes 5 (4/16), 9 (3/16), 16 (4/16) and X (4/16). These chromosomes are syntenic with human chromosomes 4, 11, 3 and X respectively (Copeland et al., 1993), all of which commonly are lost in human neuroblastoma (Plantaz et al., 1997)."

  • If this were to be done today, perhaps targeting with Wnt1 promoter in a Cre-Lox format would be more appropriate - as TH is itself in one of the amplified intervals (chr11:2043796-2201921).