Correction: Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes

  • Katleen De Preter1,

    Affiliated with

    • Jo Vandesompele1,

      Affiliated with

      • Pierre Heimann2,

        Affiliated with

        • Nurten Yigit1,

          Affiliated with

          • Siv Beckman3,

            Affiliated with

            • Alexander Schramm4,

              Affiliated with

              • Angelika Eggert4,

                Affiliated with

                • Raymond L Stallings5,

                  Affiliated with

                  • Yves Benoit6,

                    Affiliated with

                    • Marleen Renard7,

                      Affiliated with

                      • Anne De Paepe1,

                        Affiliated with

                        • Geneviève Laureys6,

                          Affiliated with

                          • Sven Påhlman3 and

                            Affiliated with

                            • Frank Speleman1Email author

                              Affiliated with

                              Genome Biology20078:401

                              DOI: 10.1186/gb-2007-8-1-401

                              Published: 31 January 2007

                               

                              We wish to report some corrections to our study [1], none of which alters the interpretation of the data or the conclusions drawn. After publication, we noticed that one of the micro-array hybridizations (on sample NB11) was performed on the same patient's material as another hybridization (sample NB4; see Table 1; a corrected version of Table 5 [1]). As this error leads to an incorrect subclassification of the patients into the 'favourable' and 'unfavourable' neuroblastoma subgroups, we would like to exclude this data point from the differential expression analysis of favorable versus unfavorable neuroblastoma given under the heading 'Differential expression analysis of favorable and unfavorable neuroblastoma' in the Results section of [1]. Careful reanalysis after exclusion of NB11 did not lead to important changes in the generated gene lists and conclusions; the changes are given in the corrected paragraph and Table 2 (a corrected version of Table 4 [1]), and the Additional data files 1 and 2 (corrected versions of Additional data files 2 and 3 [1]) available online with this article.
                              Table 1

                              Clinical and genetic data of carefully selected neuroblastoma samples that were included in this study

                              Sample number

                              Lab number

                              % Tumor cells

                              Stage

                              MYCN amp

                              Ploidy

                              Adrenal localization

                              Age

                              Dead/alive

                              Overall survival (months)

                              Type

                              NB1

                              98T33

                              95

                              1

                              No

                              Tri

                              Yes

                              < 1 year

                              Alive

                              76.9

                              Favorable

                              NB2

                              99T84

                              90

                              1

                              No

                              Tri

                              No

                              < 1 year

                              Alive

                              71.8

                              Favorable

                              NB3

                              96T82

                              90

                              1

                              No

                              Tri

                              Yes

                              < 1 year

                              Alive

                              115.5

                              Favorable

                              NB4

                              99T129

                              90

                              1

                              No

                              Tri

                              Yes

                              < 1 year

                              Alive

                              71.7

                              Favorable

                              NB5

                              01T28

                              90

                              4

                              Yes

                              Di

                              Yes

                              > 1 year

                              Dead

                              5.6

                              Unfavorable

                              NB6

                              03T304

                              100

                              3*

                              No

                              Di

                              Abdominal

                              > 1 year

                              Alive

                              12.0

                              Unfavorable

                              NB7

                              03T236

                              90

                              4

                              No

                              ND

                              Yes

                              > 5 year

                              Dead

                              19.4

                              Unfavorable

                              NB8

                              00T54

                              70

                              1

                              No

                              Tri

                              Yes

                              < 1 year

                              Alive

                              62.6

                              Favorable

                              NB9

                              00T35

                              >95

                              4

                              Yes

                              Di

                              Yes

                              < 1 year

                              Dead

                              13.7

                              Unfavorable

                              NB10

                              99T125

                              80

                              3

                              No

                              Di

                              Yes

                              > 5 year

                              Alive

                              79.3

                              Unfavorable

                              NB11 = NB4

                              99T129

                              90

                              1

                              No

                              Tri

                              Yes

                              < 1 year

                              Alive

                              71.7

                              Favorable

                              NB12

                              02T192

                              100

                              4

                              Yes

                              Di

                              Abdominal

                              > 5 year

                              Dead

                              16.2

                              Unfavorable

                              NB13

                              D031

                              >95

                              4

                              No

                              Di

                              Abdominal

                              > 1 year

                              Dead

                              64.8

                              Unfavorable

                              NB14

                              E002

                              >80

                              4

                              No

                              ND

                              Abdominal

                              > 1 year

                              Alive

                              65.7

                              Unfavorable

                              NB15

                              E037

                              >80

                              4

                              No

                              ND

                              Abdominal

                              > 1 year

                              Alive

                              45.3

                              Unfavorable

                              NB16

                              E044

                              >80

                              4

                              No

                              ND

                              Yes

                              < 1 year

                              Alive

                              37.0

                              Unfavorable

                              NB17

                              E121

                              >80

                              4

                              Yes

                              ND

                              Abdominal

                              > 1 year

                              Dead

                              78.4

                              Unfavorable

                              NB18

                              04T121

                              60

                              3

                              Yes

                              Di

                              Yes

                              > 1 year

                              Dead

                              6

                              Unfavorable

                              Samples were subdivided into favorable or unfavorable type based on MYCN amplification, ploidy and age at diagnosis. *Neuroblastoma or nodular gan-glioneuroblastoma. ND, not determined or unknown.

                              Table 2

                              Genes that are differentially expressed in favorable vs unfavorable neuroblastoma

                              Favorable NB > unfavorable NB

                              NBGS

                              Favorable NB < unfavorable NB

                              NBGS

                              neuroblast < favorable NB

                              neuroblast < favorable NB, neuroblast < unfavorable NB

                              AKAP7

                              6q

                              -

                              FABP6

                              5q

                              -

                              ARL4C

                              2q

                              -

                              IGLJ3

                              22q

                              1

                              ASPN

                              9q

                              -

                              NEFL

                              8p

                              -

                              BCL2

                              18q

                              1

                              NPY

                              7p

                              -

                              CALB1

                              8q

                              -

                              neuroblast < unfavorable NB

                              CAMK2B

                              22q

                              2

                              ALK

                              2p

                              -

                              CD24

                              6q

                              -

                              ASCL1

                              12q

                              1

                              CDC42

                              1p

                              1

                              BCL11A

                              2p

                              -

                              DDAH1

                              1p

                              -

                              BIRC5

                              17q

                              3

                              DNAPTP6

                              2q

                              -

                              C3

                              19p

                              -

                              EPB41L3

                              18p

                              1

                              CALCB

                              11p

                              -

                              FAM70A

                              Xq

                              -

                              CCL18

                              17q

                              -

                              KIFAP3

                              1q

                              1

                              CCL21

                              9p

                              -

                              OPHN1

                              Xq

                              -

                              CCNB1

                              5q

                              1

                              PPAN

                              19p

                              -

                              CD74

                              5q

                              -

                              PRKCB1

                              16p

                              1

                              CRH

                              8q

                              -

                              REEP1

                              2p

                              -

                              CSPG3

                              19p

                              -

                              RGS7

                              1q

                              2

                              CXCR4

                              2q

                              2

                              RNF11

                              1p

                              -

                              DYNC1I1

                              7q

                              -

                              SCD5

                              4q

                              2

                              F12

                              5q

                              -

                              SERINC1

                              6q

                              1

                              GFRA2

                              8p

                              -

                              ST6GALNAC5

                              1p

                              -

                              IGHA1

                              14q

                              2

                              SV2C

                              5q

                              -

                              IGHG3

                              14q

                              -

                              neuroblast > favorable NB, neuroblast > unfavorable NB

                              IGHM

                              14q

                              -

                              CACNA2D3

                              3p

                              -

                              IGKC

                              2p

                              1

                              DLK1

                              14q

                              2

                              IGLC1

                              22q

                              -

                              HBG1

                              11p

                              -

                              IGLC2

                              22q

                              -

                              HBG2

                              11p

                              -

                              LMO3

                              12p

                              1

                              neuroblast > unfavorable NB

                              MMP9

                              20q

                              1

                              ALDH3A2

                              17p

                              1

                              MYCN

                              2p

                              9

                              DBH

                              9q

                              1

                              NEFH

                              22q

                              -

                              DLC1

                              8p

                              -

                              ODC1

                              2p

                              3

                              EYA1

                              8q

                              -

                              OGDHL

                              10q

                              -

                              GCH1

                              14q

                              1

                              P2RX5

                              17p

                              -

                              HBA1

                              16p

                              -

                              PRAME

                              22q

                              1

                              HBA2

                              16p

                              -

                              RPS4Y1

                              Yp

                              1

                              NTRK1

                              1q

                              4

                              SERPINF1

                              17p

                              -

                              PTPRD

                              9p

                              -

                              SIX3

                              2p

                              -

                              PTPRK

                              6q

                              -

                              SST

                              3q

                              1

                              SFRP1

                              8p

                              1

                              TNFRSF10B

                              8p

                              2

                              SLC18A1

                              8p

                              -

                              TWIST1

                              7p

                              1

                              TFAP2B

                              6p

                              -

                              XAGE1

                              Xp

                              -

                              TLN2

                              15q

                              1

                              neuroblast > favorable NB

                                 

                              RNU2

                              17q

                              -

                                 

                              neuroblast > favorable NB, neuroblast > unfavorable NB

                                 

                              C11orf43

                              11p

                              -

                              Genes that are differentially expressed compared with neuroblasts among the differentially expressed genes in favorable neuroblastoma (NB) vs unfavorable NB, with an indication of the number of neuroblastoma microarray studies in which these genes were found through NBGS analysis. NBGS, Neuroblastoma Gene Server.

                              We also noticed that sample NB1 is stage 1 instead of stage 4S and that sample NB2 was not localized to the adrenals (see Table 1).

                              Results

                              Differential expression analysis of favorable and unfavorable neuroblastoma

                              So far, most published microarray studies on neuroblastomas mainly compared favorable with unfavorable neuroblastomas in order to identify prognostic markers or pathways that are involved in these clearly different neuroblastoma tumor types. In order to add value to such an analysis, we contrasted similar differentially expressed gene lists with the normal neuroblast expression profile (Additional data file 1). In a first step, we compared the differentially expressed genes between these two tumor types with published prognostic gene lists. We found that 23 of the 193 genes on our list were previously reported, including the well established markers MYCN, NTRK1, and CD44 (see NBGS analysis in Additional data file 2). This overlap demonstrates the validity of the selected neuroblastoma panel and their expression profile. Subsequently, we looked for the corresponding gene expression levels of the differentially expressed genes in the normal counterpart cells, aiming to select neuroblastoma candidate genes. Of the 100 genes that are more highly expressed in favorable tumors (compared to unfavorable) 41 also have a significant differential expression (either higher or lower) compared to neuroblasts, whereas 43 of the 93 genes that are more highly expressed in unfavorable tumors exhibit differential expression compared to the neuroblasts (Table 2).

                              From this analysis, a few putative positional tumor suppressor candidates emerge: CDC42 on 1p36, CACNA2D3 on 3p21 and DLK1 on 14q. The latter two genes are of particular interest because they are highly expressed in neuroblasts and favorable neuroblastomas and their expression is significantly lower in unfavorable neuroblastomas. Among the genes that are more highly expressed in unfavorable neurob-lastomas than in favorable ones and neuroblasts, the proven oncogenic transcription factor MYCN emerges (and putative downstream genes KIFAP3, OPHN1, RGS7, ASCL1, ODC1, TWIST1 and TYMS, according to NBGS), as well as several other genes that have been identified or studied in the context of neuroblastoma such as ALK and PRAME, and positional candidates on 17q including BIRC5 and RNU2.

                              Additional data files

                              Additional data files 1 and 2 containing the corrected data available online with this article.

                              Declarations

                              Authors’ Affiliations

                              (1)
                              Center for Medical Genetics, Ghent University Hospital
                              (2)
                              Department of Medical Genetics, University Hospital Erasme
                              (3)
                              Division of Molecular Medicine, Department of Laboratory Medicine, Lund University, University Hospital MAS
                              (4)
                              Department of Pediatric Oncology and Hematology, University Hospital of Essen
                              (5)
                              Children's Cancer Research Institute, University of Texas Health Science Center
                              (6)
                              Department of Pediatrics, Ghent University Hospital
                              (7)
                              Department of Pediatrics, UZ Gasthuisberg

                              References

                              1. De Preter K, Vandesompele J, Heimann P, Yigit N, Beckman S, Schramm A, Eggert A, Stallings RL, Benoit Y, Renard M, et al.: Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes. Genome Biol 2006, 7:R84.View ArticlePubMed

                              Copyright

                              © BioMed Central Ltd 2007

                              Advertisement