Kaplan-Meier survival analysis according to anatomical classifications of primary tumors.

<p>Event-free survival (EFS) and overall survival (OS) according to the anatomical compartment (a, b) and sympathetic system origin (c, d) of the primary tumor.</p

Imaging phenotypes of chest neuroblastomas.

<p><b>(a, b, c)</b> Newborn with L2-stage left posterior <b>mediastinal NCA neuroblastoma</b>. MRI at diagnosis (a, b: sagittal and axial T2-weighted sequences). The primary tumor is a unique well-delineated mass (*) with focal contact with the thoracic aorta (arrowhead) and intra-spinal extension (arrow). Follow-up MRI 3 months later (c) after neoadjuvant chemotherapy (2 courses of cyclophosphamide-vincristine and 2 courses of etoposide-carboplatin) shows the tumor residue precisely located at the costo-vertebral junction, i.e., a paravertebral sympathetic chain location. <b>(d, e)</b> 9-year-old girl with M-stage <b>mediastinal SCA neuroblastoma</b>. Enhanced CT scan at diagnosis (axial and coronal views). The primary tumor (*) is ill-defined and diffusely infiltrates the posterior mediastinum, pleura and chest wall (arrows), crosses the midline and encases the thoracic aorta (arrowhead). The presumed origins are the mediastinal sympathetic fibers surrounding the descending aorta.</p

Study cohort characteristics and relationships between patient age, INPC, stage and genomic profile.

<p>Study cohort characteristics and relationships between patient age, INPC, stage and genomic profile.</p

Radiogenomics classification of neuroblastomas according to anatomical origin.

<p>Neuroblastomas may be classified based on the anatomical compartment (i.e., neck, chest, abdomen or pelvis) or according to the sympathetic structure the tumors arise from, i.e., (1) the cervical sympathetic chains (i.e., including the superior, middle and inferior cervical and the cervicothoracic ganglia (g.)); (2) the paravertebral (PV) sympathetic chains (i.e., including all thoracic, lumbar and sacral ganglia); (3) the periarterial (PA) sympathetic pathways (i.e., including the thoracic aortic, abdominal aortic and celiac plexus (pl.)), the aorticorenal ganglia, and the superior and inferior mesenteric, superior hypogastric and iliac plexus); and (4) the adrenal glands. For each compartment or sympathetic group, the pie charts show the distribution of the genomic profile of the tumors, i.e., numerical-only chromosome alterations (NCA), segmental chromosome alterations (SCA) or <i>MYCN</i> amplification (MNA).</p

Relationships between imaging phenotypes of neuroblastomas and outcome (univariate analysis).

<p>Relationships between imaging phenotypes of neuroblastomas and outcome (univariate analysis).</p

Generation of MITF-A transgenic mice.

<p><b>A)</b> Schematic representation of the Ksp-cadherin-FLAG-MITF-A transgene. <b>B)</b> <i>Mitf-A</i> mRNA expression evaluated by quantitative RT-PCR in kidneys from wild-type (WT), heterozygous (HE) and homozygous (HO) MITF-A transgenic mice (line 42) 2 months after birth. Data are means ± SEM; n = 4–6 per each genotype. ANOVA followed by Tukey-Kramer test; transgenic <i>versus</i> wild-type mice: ** P < 0.01, *** P < 0.001. <b>C)</b> MITF-A protein expression evaluated by western blot on kidney nuclear protein extracts from WT, HE and HO MITF-A transgenic mice 2 months after birth. This is a representative image of three experiments. Nuclear protein extracts from <i>Mitfa</i>^-/- kidneys were used as a negative control; crude extracts from renal cells transfected with either FLAG-MITF-A plasmid (lane 1) or MITF-A plasmid (lane 2) were used as a positive control. Lamin A/C was used as control of nuclear protein amount. IB = immunoblot.</p

Characterization of MITF-A transgenic mice.

<p>Characterization of MITF-A transgenic mice.</p

Relationship between anatomical primary tumor location (compartment and sympathetic origin) of neuroblastomas and their genomic profile.

<p>Relationship between anatomical primary tumor location (compartment and sympathetic origin) of neuroblastomas and their genomic profile.</p

Imaging phenotypes of abdominal neuroblastomas.

<p><b>(a)</b> 18-month-old girl with M-stage right <b>adrenal MNA neuroblastoma</b>. Enhanced CT scan at diagnosis. The primary tumor (<b>*</b>) is centered on the right adrenal gland between the right kidney and the inferior vena cava (arrow) and extends medially in contact with the aorta (arrowhead). <b>(b)</b> 12-month-old girl with M-stage retroperitoneal <b>periarterial SCA neuroblastoma</b>. Enhanced CT scan at diagnosis. The primary tumor (<b>*</b>) is centered in the median retroperitoneum around the aorta (arrowhead) and behind the inferior vena cava (arrow). <b>(c)</b> Newborn with L2-stage lumbar dumbbell <b>paravertebral NCA neuroblastoma</b>. Axial T2-weighted MRI at diagnosis. The primary tumor (<b>*</b>) is centered on the right paravertebral chain and invades the psoas and spinal muscles and fills the spinal canal, compressing the spinal cord (dotted arrow). The tumor is totally separated from the inferior vena cava (arrow) and the aorta (arrowhead).</p

Expression pattern of MITF-A during kidney development.

<p><b>A-B)</b><i>In situ</i> hybridization of <i>Mitf-A</i> of E13.5 kidneys from wild-type (WT) and homozygous (HO) MITF-A transgenic embryos using an antisense RNA probe directed against a sequence encompassing exon 1A, specific for <i>Mitf-A</i>, and exon 1B common to <i>Mitf-A</i>, <i>Mitf-H</i>, <i>Mitf-C</i>, <i>Mitf-J</i> and <i>Mitf-Mc</i> isoforms. The inset shows the staining of E13.5 kidneys using the sense RNA probe. Magnifications are X100 (left panels), X200 (middle panels) and X400 (right panels). In WT kidneys <b>(A)</b> a weak staining is observed in branches of UB (black arrow), in S-shaped body (blue arrow) and in metanephric mesenchyme (asterisk). Consistent with the use of the Ksp-cadherin promoter, the signal in MITF transgenic kidneys <b>(B)</b> was strongly increased in UB and tips (black arrow), in ureteric tip (black arrow) and to a lesser extent in S-shaped body (blue arrow). <b>C)</b> <i>In situ</i> hybridization of <i>Mitf-A</i> in transgenic HO kidneys after laminin immunohistochemistry (red). Note <i>Mitf</i> expression in ureteric bud and tip (black arrow), in and S-shaped body (blue arrow). Magnification X400. Sections are representative images of 4 kidneys per genotype. <b>D</b>) Immunostaining of MITF-A in WT and HO MITF-A transgenic metanephroi at E13.5. Note the increase of MITF-A expression in UB stalks, tips and S-bodies. Magnification X400.</p