Patient with t(4;12)(q11;p13) with therapy-related MDS and known history of stage II metastatic colorectal cancer

Elizabeth Callahan, Roger Schultz, Theresa C Brown  

CSI Laboratories, 2580 Westside Parkway, Alpharetta, GA 30004, USA (EC, TCB); Signature Genomic Laboratories, Perkin Elmer Inc., Spokane, WA 99207, USA (RS)

Previous history

Preleukaemia
-
Malignant disease
+ Patient diagnosed with rectal cancer 8/03 treated with surgery and adjuvant chemo and radiation therapy. 9/2008 stage II isolated metastatic colorectal cancer involving the lung. Patient was treated with surgical resection and 5FU therapy and radiation. Patient is currently in remission. Has sibling with renal cell carcinoma.
Inborn condition
-

Clinics case report

Age
63 yrs
Sex
F
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-

Blood data

Wbc
7.8
Hb
11.2
Platelets
176
Blasts
18 18-29% bone marrow/ 4% peripheral blood
Bone marrow
28.3% segmented neutrophils, 10% eosinophils, 48.5% lymphocytes, 12.1% monocytes, 1.0% myelocytes, 2.0% metamyelocytes, and 3.0% atypical lymphocytes.

Cyto path

Cytology
Trilineage dyspoiesis consistent with myelodysplasia.
Immunophenotype
CD7: 44.4%, CD13: 67.5%, CD34: 28.7%, CD117: 30.9%, HLA-DR: 38.5%, CD38: 71.4%.
Rearranged ig tcr
n/a
Pathology
Flow cytometric analysis of the specimen labeled bone marrow reveals a significant population of myeloblasts (approximately 29% of cells that could be studied in the sample) with most expressing abnormal CD7 (up to 1/3 is CD7 negative), CD13, CD33 (expression ranges from essentially undetectable up to moderately positive), CD34, CD38, CD45, CD117, and HLA-DR. Approximately half of the blast population is above the negativity threshold and shows dim to moderate intensity, CD123 expression. The remaining myeloid cells show minor abnormalities in antigen expression with respect to acquisition of full intensity CD13 and CD16. The change is less than typically occurs in well-defined MDS cases.
Electron microscopy
n/a
Precise diagnosis
Flow cytometry- Acute myelogenous leukemia with ~29% myeloblasts. Morphology- therapy-related myelodysplasia with 18% blasts.

Survival data

Date diagnosis
07-2010
Treatment
Patient is being treated with Vidasia, induction chemotherapy and salvage chemotherapy.
Complete remission
Refractory AML s/p chemotherapy.
Treatment relat death
n/a
Relapse
n/a
Status
A
Date last follow
03-2012
Survival
20

Karyotype

Sample
Bone marrow
Culture time
24 culture (unstimulated) and 48 hour culture (unstimulated).
Banding
GTW
Results
46,XX,t(4;12)(q11;p13)[20]
Karyotype relapse
n/a
Mol cytogenet technics
Interphase FISH using Vysis LSI 4q12 Tricolor Rearrangement Probe (Abbott). Interphase FISH using LSI break apart probe for ETV6 (Abbott) was attempted on destained slides, no signals were detected.
Mol cytogenet results
nuc ish(SCFD2,LNX,PDGFRA,KIT)x2 (SCDF2 con LNX sep PDGFRA,KITx1).

Other molec studies

Technics
OncoChip™ / CNE. Microarray analysis using a whole genome oligonucleotide array, which specifically targets genes, micro RNAs and specific genomic intervals with known or suspected relevance to cancer.
Results
Unclear findings. arr 7q34(141,693,456-141,719,136)x4,14q32.33(105,949,400-105,987,288)x0~1. Finding TCR and IGH rearrangements in the same clone is not unheard of as there is crosstalk. CNE hasn t been validated as a test for clonality.

Images

Atlas Image
Fig. 1: Rare t(4;12)(q11;p13) found in a female patient with known history of metastatic colorectal cancer presenting with secondary high grade myelodysplastic syndrome.
Atlas Image
Fig. 2: Confirmation of 4q12 rearrangement using Vysis LSI 4q12 Tricolor Rearrangement Probe (Abbott).

Comments section

Comments
Rare t(4;12)(q12;p13) found in a 63 year old female with history of stage II isolated metastatic colorectal cancer involving the lung. Results were confirmed by interphase FISH utilizing Vysis 4q12 Tricolor Rearrangement Probe (Abbott). Microarray studies were conducted using OncoChip™ whole genome oligonucleotide array, and yielded the following results: CNE result arr(1-22,X)x2 Normal Female, result with unclear clinical significance: arr 7q34(141,693,456-141,719,136)x4,14q32.33(105,949,400-105,987,288)x0~1.

Bibliography

Pubmed IDLast YearTitleAuthors
75454251995A specific chromosome abnormality of t(4;12)(q11-12;p13) in CD7+ acute leukaemia.Harada H et al
91306131997Characterization of acute leukemia with t(4;12).Harada H et al
118612952002Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13).Cools J et al
125312292003t(4;12)(q11;p13): a rare chromosomal translocation in acute myeloid leukemia.Chauffaille Mde L et al
201071582010Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis.Erben P et al
205135382010A rare t(4;12)(q12;p13) in an adolescent patient with acute myeloid leukemia.Manabe M et al

Citation

Elizabeth Callahan, Roger Schultz, Theresa C Brown

Patient with t(4;12)(q11;p13) with therapy-related MDS and known history of stage II metastatic colorectal cancer

Atlas Genet Cytogenet Oncol Haematol. 2012-09-01

Online version: http://atlasgeneticsoncology.org/case-report/208863/patient-with-t(4;12)(q11;p13)-with-therapy-related-mds-and-known-history-of-stage-ii-metastatic-colorectal-cancer