Acta Neuropathologica
SUPPLEMENTARY INFOMRATION
Pituitary Blastoma: a pathognomonic feature of germ-line DICER1 mutations
AUTHORS:
Leanne de Kock1,2, Nelly Sabbaghian2, François Plourde2, Archana Srivastava2, Evan Weber3,
Dorothée Bouron-Dal Soglio4, Nancy Hamel3,5, Joon Hyuk Choi6, Sung-Hye Park7, Cheri L.
Deal8, Megan Dishop9, Adam Esbenshade10, John F. Kuttesch11,28, Thomas S. Jacques12, Arie
Perry13, Heinz Leichter14, Philippe Maeder15, Marie-Anne Brundler16,29, Justin Warner17, James
Neal18, Margaret Zacharin19, Márta Korbonits20, Trevor Cole21, Heidi Traunecker22, Thomas W.
McLean23, Fabio Rotondo24, Pierre Lepage25, Steffen Albrecht26, Eva Horvath24, Kalman
Kovacs24, John R. Priest27 and William D. Foulkes1,2,3,5
Correspondence to: Dr. William D. Foulkes at the Department of Medical Genetics, The Lady Davis
Institute, Segal Cancer Centre, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal,
QC, Canada, H3T 1E2. Email: william.foulkes@mcgill.ca. Tel: (+1) 514-340-8222 Ext. 3213.
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SUPPLEMENTARY INFOMRATION
SUPPLEMENTARY TABLES
Supplementary Table S1: DNA sample source, sequencing method and mutation summary
Supplementary Table S2: Fluidigm Access Array Custom Design Primers
Supplementary Table S3: Primer Sequences for loss of heterozygosity analysis
Supplementary Table S4: DICER1 Mutations and Traces
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SUPPLEMENTARY FIGURES
SUPPLEMENTARY FIGURE S1: Case 3
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Supplementary Figure S1: Case 3 Legend:
A: Case 3: The proband (individual IV-3), a carrier of the c.2379T>G germ-line DICER1
mutation, was diagnosed with a PitB at the age of 9 months. Thirteen family members,
including the proband, tested positively for the germ-line DICER1 mutation. Individuals
shaded in black have known DICER1-related lesions. Individuals shaded in grey have other
cancers not suspected to be related to DICER1 syndrome. Abbreviations: CN, cystic
nephroma; MNG, multinodular goitre; PPB, pleuropulmonary blastoma; SLCT, Sertoli
Leydig cell tumour.
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SUPPLEMENTARY FIGURE S2: Case 4
Supplementary Figure S2: Case 4 Legend: The proband, individual III-1, was diagnosed with a
PitB at the age of 18 months. Both the proband and her mother (individual II-2) were found to carry
the c.3535_3538delTCTT DICER1 germ-line mutation. The maternal grandmother, individual I-2
died of leukaemia at the age of 33 years. Individuals I-3, I-4 and I-5 had hypothyroidism.
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SUPPLEMENTARY FIGURE S3: Case 5
Supplementary Figure S3: Case 5 Legend: At the age of 13 months, the female proband (individual
III-1) was diagnosed with a PitB. She was found to be a carrier of a de novo germ-line DICER1
mutation (c.1525C>T, p.(Glu1809Trp)).
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SUPPLEMENTARY FIGURE S4: CASE 9
Supplementary Figure S4: Case 9 Legend: The female proband (individual III-2), a carrier of the
c.2026C>T germ-line DICER1 mutation, was diagnosed with a PitB at 7 months of age. Additionally,
individual I-2 had colon cancer and individual III-4 (a carrier), had a thyroid carcinoma. Individuals
II-2 and II-4 were also found to be carriers of the segregating mutation.
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SUPPLEMENTARY FIGURE S5: CASE 11
Supplementary Figure S5: Case 11 Legend: At 9 months of age, the female proband (individual III2) was diagnosed with a PitB. She was found to carry a c.1284delGA germ-line DICER1mutation.
Both mother (individual II-2) and maternal grandmother (individual I-2, deceased) were found to be
carriers of the same germ-line mutation and a second somatic DICER1 RNase IIIb mutation
(c.5437G>C, p.(Glu1813Gln)) was identified with the Sertoli Leydig cell tumour (SLCT) harboured
by the grandmother (diagnosed at 54 years). The grandmother also had a history of pulmonary bullae.
The mother was reported to have had a thyroid nodule at 18 years of age and individual I-3 (deceased)
had a brain carcinoma at 26 years.
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SUPPLEMENTARY FIGURE S6: CASE 13
Supplementary Figure S6: Case 13 Legend: The 9-month-old female infant (individual IV-1) was
diagnosed with a PitB. Individual I-3 had a throat carcinoma, leukaemia (AML) and Type 2 diabetes
and individual III-4 (a half-brother of individual II-5) had a bladder carcinoma at 50 years of age.
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SUPPLEMENTARY FIGURE S7:
Supplementary Figure S7 Legend:
Short tandem repeat (STR) marker genotyping performed on case 13 to identify loss of heterozygosity
in the tumour. Alleles are highlighted to the left of each image: black is the conserved allele, red is the
allele lost in the tumor. LOH is evident in the tumour at STR markers D14S1054 and D14S265. The
reference
used
is
hg19
obtained
from
the
UCSC
Genome
Browser
(http://genome.ucsc.edu/index.html).
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