Table 4 Summary of studies that reported on heterogeneous MYCN amplification in NB

From: Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study

Study

n cases (%)

Technique

Sample (n cases)

HetMNA

Age >/<18 months (n)

Stage (n)

Outcome (n)

    

Patterns

Features (MYCN copies)

   

Squire et al., 1996

5/29 (17.2)

FISH, SB, PCR

PT

Intratissue

2/5 with small number of MNA cells (3–10)

NR

NR

NR

Lorenzana et al., 1997

1

FISH, SB

PT & CTX

Intratissue

GNB: MNA u-nbs (15–20), nonMNA d-nbs

>

3

DOD

Ambros et al., 2001

3/300 (1)

FISH

PT

Intratissue

Focal MNA (10–50)

NR

1 (2), 4s (1)

NR

Kerbl et al, 2002

1

FISH

PT

Intratissue

Focal MNA (>15)

<

NR

ADF

Noguera et al., 2003

1

FISH

PT & R

Temporal

PT: MNG, R: homMNA

<

4s

DOD

Valent et al., 2004

4/200 (2)

FISH, Q-PCR

PT (4), BM (1)

Intratissue & spatial

MNA and MNG cells; PT: homMNA, BM: MNG

NR

4s (2), 3 (1), 4 (1)

ADF (1) AWT (2) DOT (1)

Spitz et al., 2004

4/659 (<1)

FISH

PT (2), BM (1), CTX (1)

Intratissue, spatial & temporal

Focal and scattered MNA; PT/BM: hetMNA, R: homMNA; PT: nonMNA, BM: MNA

NR

NR

NR

Thorner et al., 2006

4/41 (9.7)

CISH, FISH, SB, PCR

PT

Intratissue

≥50% MYCN copy number difference from cell to cell

NR

NR

NR

Sano et al., 2007

1

FISH

PT

Intratissue & spatial

Composite NB: noMNA, MNA; Lymph nodes: homMNA

<

3

AWT

Cañete et al, 2009

5/46 (10.9)

FISH

PT

Intratissue

SIOPEN cohort

<

NRa

NR

Theissen et al., 2009

20/1341 (1.5)

FISH

PT (15), PT & BM (3), PT & R (2)

Intratissue, spatial & temporal

Focal & scattered MNA; PT: hetMNA,

R: nonMNA/hetMNA/homMNA;

PT: nonMNA/homMNA, R:hetMNA/homMNA;

PT: nonMNA,

BM: nonMNA/hetMNA,

R: hetMNA/homMNA

< (9) & > (11)

(2), 4s (3), 3 (6), 4 (9)

ADF (7) Prog. (4) DOD (9)

Bishop et al., 2014

1

FISH

PT

Intratissue, spatial

Focal MNA;

adrenal mass: hetMNA,

Liver: homMNA

<

4s

ADF

Berbegall et al., 2016

3

FISH, aSNP

PT

Intratissue, spatial & temporal

Iliac crests: nonMNA and MNA;

BM: nonMNA, metastases: hetMNA

>

4

Prog.

Marrano et al., 2017

8/30 (26.7)

qPCR, FISH, CISH

PT/CTX (4),

PT & R (1), M (1),

CTX & R/M (2)

Intratissue, spatial & temporal

Changes in the MYCN copy number (reduction or increase)

< (2) & > (5)

(6)

DOD (6), A (2)

  1. Note: studies of recently published patient cohorts with hetMNA tumours corresponding to refs. 25,27 are not included
  2. n number, FISH fluorescence in situ hybridisation, PCR polymerase chain reaction, qPCR quantitative PCR, SB Southern blot, aSNP SNP array, ADF alive disease free, AWT alive with treatment, A alive, CISH chromosome in situ hybridisation, CTX post-chemotherapy biopsy, d-nbs differentiated neuroblasts, DOD dead of disease, GNB ganglioNB, MNA MYCN amplification, homMNA homogeneous MNA, L localised, MNG MYCN gain, pd-nbs poorly differentiated neuroblasts, NR not reported, Prog. progression, PT primary tumour, biopsy, M metastasis biopsy at diagnosis, u-nbs undifferentiated neuroblasts
  3. aother than stage 1