Universität zu Köln

Hoell, J. I., Gombert, M., Ginzel, S., Loth, S., Landgraf, P., Kaefer, V., Streiter, M., Prokop, A., Weiss, M., Thiele, R. and Borkhardt, A. (2014). Constitutional Mismatch Repair-deficiency and Whole-exome Sequencing as the Means of the Rapid Detection of the Causative MSH6 Defect. Klinische Padiatr., 226 (6-7). S. 357 - 362. STUTTGART: GEORG THIEME VERLAG KG. ISSN 1439-3824

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Abstract

Background: Cases of children with more than one type of cancer either diagnosed simultaneously or successively, rarely occur in pediatric oncology. A second malignant neoplasm may be caused by mutagenic effects of the treatment of the primary malignancy and/or may point towards an underlying genetic cancer susceptibility syndrome. One example of such a syndrome is constitutional mismatch repair-deficiency, (CMMR-D) which carries an increased risk of various tumors including childhood hematologic malignancies and Lynch syndrome associated tumors. Timely diagnosis of CMMR-D is crucial, since this diagnosis has implications for the entire family. Patient: We report the case of a 15-year-old girl who was born to consanguineous parents. At the age of 20 months she was diagnosed with a T-cell non-Hodgkin lymphoma. Treatment was given according to NHL-BFM 95. 12 years later, an invasive adenocarcinoma of the colon was surgically removed which relapsed shortly afterwards. Methods: Whole-exome sequencing of germline DNA was employed to rapidly detect the underlying mutation in this suspected CMMR-D patient. Results: After a short turnaround time of less than 3 weeks, the diagnosis of CMMR-D could be confirmed by the identification of a homozygous 29-bp deletion in MSH6 (exon 6), which was confirmed by independent methods. Conclusions: We demonstrate that bed-side whole-exome sequencing is both feasible and cost-effective and may be the method of choice to rapidly uncover the genetical basis of (inherited) diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoell, J. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gombert, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ginzel, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Loth, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Landgraf, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaefer, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Streiter, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Prokop, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borkhardt, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423915
DOI:	10.1055/s-0034-1389905
Journal or Publication Title:	Klinische Padiatr.
Volume:	226
Number:	6-7
Page Range:	S. 357 - 362
Date:	2014
Publisher:	GEORG THIEME VERLAG KG
Place of Publication:	STUTTGART
ISSN:	1439-3824
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EUROPEAN CONSORTIUM CARE; NEXT-GENERATION; MUTATIONS; VARIANTS; CANCER; IDENTIFICATION; DISORDERS; CHILDHOOD Multiple languages Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42391