PMC4272944_01
High-resolution single nucleotide polymorphism array (HR SNP-A) analysis results for chromosome 9 (A) and 13 (B) performed at diagnosis in Case 1. Deleted lesions are indicated with a red box, and detailed array results in each lesion are provided. The results showed a homozygous 1,944 kb deletion of 9p21.3, including CDKN2A; a 96 kb deletion of 13q14.2, including RB1; and a heterozygous 5,262 kb deletion of 9p21.3p21.2. The FISH analysis for the detection of RB1 deletion at diagnosis showed nuc ish (RB1,13q34)x2[200], which indicates no deletion of RB1(C). Identical HR SNP-A analysis results for chromosome 9 (D) and 13 (E) performed at relapse in Case 1 showed a heterozygous 1,752 kb deletion of 9p21.3, including CDKN2A and an 89 kb deletion of 13q14.2, including RB1. FISH analysis for the detection of RB1 deletion at relapse also showed nuc ish (RB1,13q34)x2[200], which indicates no deletion of RB1(F).
alm-35-132-g001.jpg
PMC4272944_01_alm-35-132-g001.jpg
F1
Affymetrix Cytogenetics 2.7M Array (Affymetrix; Santa Clara, CA, USA) with bone marrow samples obtained both at diagnosis and relapse. At diagnosis, SNP-A analysis revealed homozygous deletions of 9p21.3 (associated with CDKN2A) and 13q14.2 (associated with RB1) and heterozygous deletions of 6p22.2, 8q22.1, 9p21.3p21.2, 14q11.2, 18q22.2, and 19p13.2 (Fig. 1A, B). FISH analysis for the detection of RB1 deletions showed nuc ish (RB1,13q14)x2[200] (Fig. 1C). An identical assay performed at relapse showed loss of heterozygous deletions in 6 affected lesions along with subtle size changes in deleted lesions of 9p21.3 (1,944-1,752 kb) and 13q14.2 (96-89 kb), indicating the persistence of CDKN2A and RB1 deletion at relapse (Fig. 1D, E). FISH analysis for the detection of RB1 deletions also showed nuc ish (RB1,13q14)x2[200] (Fig. 1F).
PMC4272944_02
High-resolution single nucleotide polymorphism array (HR SNP-A) analysis results in whole chromosomes at diagnosis (idiograms of six chromosomes harboring aberrations are provided) in Case 2 (A). The array results showed heterozygous interstitial deletions of 3q13, 4q23q24, 5q15q21.3, 5q21.3q22.1, 5q22.3q23.1, 5q34, 6q16.3q21, 7q11.23, and 13q14.2q14.3, including RB1 gene. Deleted lesions are indicated separately with red arrows, and the detailed array results for each lesion are provided. Identical array results for whole chromosome at relapse in Case 2 (B) showed similar results, but slight size changes in deleted genomic lesions at 3q13, 4q23q24, 5q15q21.3, 5q21.3q22.1, 5q34, and 13q14.2q14.3 were identified at relapse compared to those at diagnosis. Deleted lesions are also indicated separately with red arrows, and detailed array results for each lesion are provided. In addition, HR SNP-A analysis results of chromosome 9 performed at both diagnosis and relapse in Case 3 (C) are provided. The deleted lesion is indicated with a red box, and detailed array result is provided. The array result showed an interstitial 451 kb deletion of 9p21.3, which includes IFNA13 and MIR31 in a mosaic pattern.
alm-35-132-g002.jpg
PMC4272944_03_alm-35-132-g002.jpg
F2
HemaVision results were also negative. However, SNP-A analysis demonstrated an interstitial 451 kb deletion of 9p21.3, which includes interferon alpha-1/13 (IFNA13) and micro-RNA 31 (MIR31) in a mosaic pattern, at both diagnosis and relapse (Fig. 2C).
PMC4272944_03
High-resolution single nucleotide polymorphism array (HR SNP-A) analysis results in whole chromosomes at diagnosis (idiograms of six chromosomes harboring aberrations are provided) in Case 2 (A). The array results showed heterozygous interstitial deletions of 3q13, 4q23q24, 5q15q21.3, 5q21.3q22.1, 5q22.3q23.1, 5q34, 6q16.3q21, 7q11.23, and 13q14.2q14.3, including RB1 gene. Deleted lesions are indicated separately with red arrows, and the detailed array results for each lesion are provided. Identical array results for whole chromosome at relapse in Case 2 (B) showed similar results, but slight size changes in deleted genomic lesions at 3q13, 4q23q24, 5q15q21.3, 5q21.3q22.1, 5q34, and 13q14.2q14.3 were identified at relapse compared to those at diagnosis. Deleted lesions are also indicated separately with red arrows, and detailed array results for each lesion are provided. In addition, HR SNP-A analysis results of chromosome 9 performed at both diagnosis and relapse in Case 3 (C) are provided. The deleted lesion is indicated with a red box, and detailed array result is provided. The array result showed an interstitial 451 kb deletion of 9p21.3, which includes IFNA13 and MIR31 in a mosaic pattern.
alm-35-132-g002.jpg
PMC4272944_03_alm-35-132-g002.jpg
F2
HemaVision results were also negative. However, SNP-A analysis demonstrated an interstitial 451 kb deletion of 9p21.3, which includes interferon alpha-1/13 (IFNA13) and micro-RNA 31 (MIR31) in a mosaic pattern, at both diagnosis and relapse (Fig. 2C).