t(2;2)(p22;p22) LTBP1/BIRC6
del(2)(p22p22) LTBP1/BIRC6

2016-12-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr


Review on t(2;2)(p22;p22) and del(2)(p22p22) LTBP1/BIRC6 in acute myeloid leukemia, with data on the genes involved.

Clinics and Pathology


Only two cases to date of t(2;2)(p22;p22) or del(2)(p22p22) LTBP1/BIRC6 in acute myeloid leukemia have been described (Cancer Genome Atlas Research Network 2013; Yoshihara et al. 2015). This chromosomes and genes rearrangements have also been found in a case of breast carcinoma, and in a case of lung squamous cell carcinoma: t(2;2)(p22;p22) or del(2)(p22p22) LTBP1/BIRC6 in solid tumors.


Acute myeloid leukemia


Data were described in only one case: a 75-year old male patient presented with AML-M2. Overall survival was 0.1 month (Cancer Genome Atlas Research Network 2013).


The karyotype was normal (cryptic rearrangement).

Genes Involved and Proteins

FLT3 mutation was positive; IDH1 R132, R140, R172 were negative; activating RAS was negative; NPMc was negative.
Gene name
BIRC6 (Baculoviral IAP repeat-containing 6)
Protein description
BIRC6 contains two domains: a N-terminal BIR repeat (needed for interactions with caspases and IAP-binding motif (IBM) containing proteins) and a C-terminal UBC domain (which can form a thiolester linkage with ubiquitin transferred by E1).
1721 amino acids; belongs to the LTBP/fibrillin family.
LTBP1 is composed of a signal peptide: (amino acids 1-23), 18 epidermal growth factor (EGF)-like repeats and four cysteines rich domains, the TB (TGFb binding protein-like) domains. The LTBP1 C-terminus interacts with the extracellular matrix via fibrillin microfibrils. EGF-like repeats provide stability to the protein structure
TGFB1 is secreted as a biologically latent complex composed of LTBP1, a latency associated peptide (LAP), (LAP is the TGFB1 pro-peptide which regulates latency, that is cleaved intracellularly prior to secretion), and the TGFB1 cytokine. LTBP1 plays roles in facilitating the folding and secretion of TGFB1 from the cell, and activation.
LTBP1 interacts with FBN1 (fibrillin 1). This interaction allows LTBP1 to sequester TGFB1 to fibrillin microfibrils; EFEMP2 (EGF containing fibulin-like extracellular matrix protein 2, or fibulin4) and ADAMTSL proteins form ternary complexes with LTBP1 and fibrillin.
LTBP1 is involved in epithelial-mesenchymal interaction and epithelial differentiation (Mazzieri et al., 2005; Robertson et al., 2014).BIRC6 and autophagy: BIRC6 is required to inhibit autophagy
(Iris Luk and Wang, 2014).
BIRC6 is involved in myelodysplastic syndromes and acute myeloid leukemias, colorectal cancer, neuroblastoma, skin melanoma, non-small cell lung cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma and breast cancer.
Gene name
LTBP1 (latent transforming growth factor beta binding protein 1)
Dna rna description
Eleven splice variants.

Result of the Chromosomal Anomaly


5 LTBP1 - 3 BIRC6


Pubmed IDLast YearTitleAuthors
236349962013Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.Ley TJ et al
158701092005Expression of truncated latent TGF-beta-binding protein modulates TGF-beta signaling.Mazzieri R et al
244898522014NMR spectroscopic and bioinformatic analyses of the LTBP1 C-terminus reveal a highly dynamic domain organisation.Robertson IB et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al


Fusion gene



Jean-Loup Huret

t(2;2)(p22;p22) LTBP1/BIRC6
del(2)(p22p22) LTBP1/BIRC6

Atlas Genet Cytogenet Oncol Haematol. 2016-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1714/del(2)(p22p22)