inv(12)(p13q15) ETV6/PTPRR

2013-02-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


Myelodysplastic syndrome (MDS), and acute myeloid leukemias (AML)


A 75-year-old female patient presented with refractory anemia (RA) (Welborn et al., 2004). A 24-year-old female patient presneted with acute myelogenous leukemia (M2-AML) (Nakamura et al., 2005).


The patient with RA was alive 14 months after diagnosis without treatment. The patient with M2-AML underwent bone marrow transplantation and remained in remission 44 months after diagnosis.


Another case of inv(12)(p13q15) was that of a 59 -year-old female patient with AML M2. However, the 5 part of ETV6 was translocated to chromosome15 and the 3 part of ETV6 to 12q15 (Setoyama et al., 1998). Therefore the genetic rearrangement is different.
Only the case studied by Nakamura et al., 2005 ascertained the breakpoints within ETV6 and PTPRR.

Genes Involved and Proteins

Gene name
ETV6 (ets variant 6)
Protein description
452 amino acids. ETV6 is composed of a HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term (binds to the DNA sequence 5-CCGGAAGT-3). Transcriptional regulator; tumor suppressor. Involved in bone marrow hematopoiesis.
Gene name
PTPRR (protein tyrosine phosphatase, receptor type, R)
Protein description
657 amino acids. PTPRR belong to the protein tyrosine phosphatase (PTP) family. PTPRR is composed of a signal peptide, a hydrophobic region, a transmembrane region, a kinase interacting motif, and a protein tyrosine phosphatase domain. PTPRR isoforms are regulators of MAPK phosphorylation levels. Activated PKA prevents the PTPRR-MAPK binding and MAPK inhibition by phosphorylation of the KIM domain of PTPRR. PTPRR-deficient mice exhibit ataxic symptoms (Hendriks et al., 2009). PTPRR is down regulated in colorectal cancer (Menigatti et al., 2009).

Result of the Chromosomal Anomaly


The chimeric DNA joined ETV6 exons 1 to 4 and PTPRR exons 7 to 14.
Alternative splicing leads to generation of 10 ETV6/PTPRR chimeric cDNAs, of which a truncated ETV6, due to frameshift, and an ETV6/PTPRR in-frame isoform with an open reading frame of 1158 nucleotides coding for 385 amino acids, including the helix-loop-helix domain of ETV6 and most of the protein tyrosine phosphatase domain of PTPRR.
Atlas Image


The ETV6/PTPRR fusion protein is made of 385 amino acids (aa), including the helix-loop-helix domain of ETV6 and most of the protein tyrosine phosphatase domain of PTPRR. 154 aa come from ETV6 and 231 from PTPRR.


Both truncated ETV6 and ETV6/PTPRR were shown to affect nuclear localization of wild-type ETV6. Both can heterodimerize with wild-type ETV6. ETV6/PTPRR lacks protein tyrosine phosphatase activity. Both truncated ETV6 and ETV6/PTRPP could be important in leukemogenesis.


Pubmed IDLast YearTitleAuthors
191373822009PTPRR protein tyrosine phosphatase isoforms and locomotion of vesicles and mice.Hendriks WJ et al
200153822009The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis.Menigatti M et al
160616412005Cloning and characterization of the novel chimeric gene TEL/PTPRR in acute myelogenous leukemia with inv(12)(p13q13).Nakamura F et al
96947361998A unique translocation of the TEL gene in a case of acute myelogenous leukemia with inv(12)(p13q15).Setoyama M et al
147342192004Inversion of chromosome 12 and lineage promiscuity in hematologic malignancies.Welborn J et al


Fusion gene

ETV6/PTPRR ETV6 (12p13.2) PTPRR (12q15) M inv(12)(p13q15)


Jean-Loup Huret

inv(12)(p13q15) ETV6/PTPRR

Atlas Genet Cytogenet Oncol Haematol. 2013-02-01

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