Details of critical rearrangements concerning MCRs.

<p>A = gain on 8q24.3 in a t-AML; B = loss of 12 p13 in t-AML (patients t-4 and t-5); C loss of 3p21.3 in a p-AML.</p

Minimal critical regions in the literature including the present work: gains.

<p>The first column lists the chromosomal losses and gains. The second lists the absolute number of each rearrangement (excluding a single rearrangement). The third and the fourth are the absolute numbers in p-AML and t-AML respectively and the percentage is indicated between parenthesis. The chromosomal location is listed. The references are indicated by letters: A <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi1" target="_blank">[32]</a>, B <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi2" target="_blank">[33]</a>, C <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi3" target="_blank">[34]</a>, D <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Parkin1" target="_blank">[18]</a>, E <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Parkin2" target="_blank">[19]</a>, F <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Paulsson1" target="_blank">[28]</a>, G <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Rucker1" target="_blank">[29]</a>, H <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Suela1" target="_blank">[30]</a>, I <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Tyybakinoja1" target="_blank">[31]</a>, J <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Walter1" target="_blank">[20]</a>, K present work. The last column lists the genes included in those MCR.</p

Minimal Critical Region in the two groups of patients.

<p>Column 1, the location of the MCR that follows the rules of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone-0016623-t004" target="_blank">tables 4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone-0016623-t005" target="_blank">5</a>; the figures in brackets and in bold are the ratios of the amplified regions. Column 2, patients; the figures in bold indicate the smaller CNA.</p

p-AML (case p24) with a complex karyotype.

<p>See the amplification of 15q23q24 and of 21q11.2q22.1 that are enlarged at the gene level. Multiple abnormalities (cf <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone-0016623-t005" target="_blank">table 5</a>) are asterisked.</p

Gains and losses CNA in t-AML and revised karyotype after aCGH.

<p>Column 2 and 3: The CNA are either lost or gained as indicated by a “−” or a “+”; locations on chromosomes are described according to the ISCN 2009 with slight modifications: sequence numbers are included between <> and expressed in Mb, with a resolution of 10kb; linear ratios are written between brackets after an “×”; CNAs with a linear ratio >2 (low level of amplification) or losses <0.25 are labeled in <b>bold</b> and <b><i>italics</i></b>; “*” indicates CNA that are probably part of a rearrangement of the immunoglobulin genes. They have not been included in the synthetic karyotypes because they could be considered as an acquired CNV which is characteristic of monoclonal proliferation.</p><p>Column 4: In <b>bold</b> are new data or those modified by aCGH in the synthetic karyotypes; CNAs that were contiguous but whose ratios were not too different were fused to express overall chromosome abnormality for readability.</p

Minimal critical regions in the literature including the present work: losses.

<p>The first column lists the chromosomal losses and gains. The second lists the absolute number of each rearrangement (excluding a single rearrangement). The third and the fourth are the absolute numbers in p-AML and t-AML respectively and the percentage is indicated between parenthesis. The chromosomal location is listed. The references are indicated by letters: A <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi1" target="_blank">[32]</a>, B <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi2" target="_blank">[33]</a>, C <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Akagi3" target="_blank">[34]</a>, D <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Parkin1" target="_blank">[18]</a>, E <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Parkin2" target="_blank">[19]</a>, F <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Paulsson1" target="_blank">[28]</a>, G <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Rucker1" target="_blank">[29]</a>, H <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Suela1" target="_blank">[30]</a>, I <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Tyybakinoja1" target="_blank">[31]</a>, J <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016623#pone.0016623-Walter1" target="_blank">[20]</a>, K present work. The last column lists the genes included in those MCR.</p

Gains and losses CNA in p-AML and revised karyotype.

<p>Column 2 and 3: The CNA were either lost or gained as indicated by a “−” or a “+”; the locations on the chromosomes are described according to the ISCN 2009 with slight modifications: sequence numbers are included between <> and expressed in Mb, with a resolution of 10kb; linear ratios are written between brackets after an “×”; CNAs with a linear ratio >2 (low level of amplification) or losses <0.25 are labeled in <b>bold</b> and <b><i>italics</i></b>; “*” indicates CNA that are probably part of a rearrangement of the immunoglobulin genes. They are not included in the synthetic karyotypes as they could be considered as an acquired CNV characteristic of monoclonal proliferation.</p><p>Column 4: In <b>bold</b> are new data or those modified by aCGH in the synthetic karyotypes; CNAs that were contiguous but whose ratios were not too different were fused to express overall chromosome abnormality for readability.</p

aCGH karyogram of patient t-8 and MCR delineation of RUNX1.

<p>A = A del (7q) and trisomy 13 are obvious. Cryptic deletions from 21q22.1 (corresponding to RUNX1) and from Xp11.4, that are smaller than 60kb, are nullosomic. On 22q11, the loss is a constitutive CNV of GGT1. B = A UCSC map (build 18) of the RUNX1 gene. C = The deletions of RUNX in four patients at the molecular level are labeled in orange and the smallest in red. The location of the breakpoints are indicated at the ends of the colored lines. Patient t-8 exhibits a homozygous 590 Kb deletion that encompassed the entire RUNX1 gene and could have occurred by an acquired isodisomy. Patient t-11 had the smallest deletion (40Kb) that was internal to RUNX1; t-29 had a deletion limited to RUNX1.</p

Clinical, biological features and karyotype of the p-AML patients.

<p>1 = age at diagnosis of AML. FAB column: FAB classification. FISH column: MLL WT = MLL Wild Type; MLL sep = MLL rearranged (separated); PML-RARA fus = fusion of PML and RARA gene; WCP = whole chromosome paint; ND = Not Done.</p

Clinical, biological features and karyotype of t-AML patients.

<p>1 = patients. 2 = age at diagnosis of AML. 3 = Primary cancer; NHL: Follicular non hodgkin lymphoma, NSCLC: Non small cell lung cancer, VLSL: Villositary lymphocyte splenic lymphoma. 4 = Primary cancer treatment; Alk: alkylating agent, RT: radiotherapy, AT II: anti-topoisomerase II, AM: anti-metabolite, brachy: brachytherapy, Clo: Chlorambucyl, Tax: taxane, Fluda: fludarabine, SP: platinium, Bleo: bleomycin, HT: hormonotherapy, INF: interferon, Rit: Rituximab, RT: Radiotherapy, TBI: Total Body Irradiation, Oncov: Oncovin, A: alkylating-agent-inducing type, T: anti-topoisomerase-inducing type, U: undetermined. 5 = FAB classification: biph = biphenotypic. 6 = FISH column: MLL WT = MLL Wild Type, MLL R = MLL rearranged, ND = Not Done. 7 = Type of t-AML; A: alkylant induced, T anti-topoisomerase-induced. 8 = AML treatment. 9 = Allograft as treatment.</p>#<p>This patient had secondary MDS for several years before the leukemia, with transitory partial monosomy 7, that had disappeared a year later, two years later the t-AML appeared.</p