Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.

نویسندگان

  • Silva Saarinen
  • Mervi Aavikko
  • Kristiina Aittomäki
  • Virpi Launonen
  • Rainer Lehtonen
  • Kaarle Franssila
  • Heli J Lehtonen
  • Eevi Kaasinen
  • Peter Broderick
  • Jussi Tarkkanen
  • Barbara J Bain
  • Frédéric Bauduer
  • Ali Ünal
  • Anthony J Swerdlow
  • Rosie Cooke
  • Markus J Mäkinen
  • Richard Houlston
  • Pia Vahteristo
  • Lauri A Aaltonen
چکیده

A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

NPAT mutations in Hodgkin lymphoma.

Hodgkin lymphoma is one of the most frequent lymphomas in the Western world. Based on differences in tumor cell morphology and phenotype and the histologic picture, this lymphoma entity is subdivided into a classic form and NLPHL, the former accounting for about 95% of cases. We know relatively little about the genetic lesions causing Hodgkin lymphoma, partly because of the rarity of the tumor ...

متن کامل

Whole Exome Sequencing Reveals a BSCL2 Mutation Causing Progressive Encephalopathy with Lipodystrophy (PELD) in an Iranian Pediatric Patient

Background: Progressive encephalopathy with or without lipodystrophy is a rare autosomal recessive childhood-onset seipin-associated neurodegenerative syndrome, leading to developmental regression of motor and cognitive skills. In this study, we introduce a patient with developmental regression and autism. The causative mutation was found by exome sequencing. Methods: The proband showed a gener...

متن کامل

Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene.

Hodgkin lymphoma shows strong familial aggregation but no major susceptibility genes have been identified to date. The goal of this study was to identify high-penetrance variants using whole exome sequencing in 17 Hodgkin lymphoma prone families with three or more affected cases or obligate carriers (69 individuals), followed by targeted sequencing in an additional 48 smaller HL families (80 in...

متن کامل

Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

Background: Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP. Methods: The proband (index patient) had polyuria, polyd...

متن کامل

Exome sequencing reveals germline gain-of-function EGFR mutation in an adult with Lhermitte–Duclos disease

Lhermitte-Duclos disease (LDD) is a rare cerebellar disorder believed to be pathognomonic for Cowden syndrome. Presently, the only known etiology is germline PTEN mutation. We report a 41-yr-old white female diagnosed with LDD and wild-type for PTEN. Exome sequencing revealed a germline heterozygous EGFR mutation that breaks a disulfide bond in the receptor's extracellular domain, resulting in ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Blood

دوره 118 3  شماره 

صفحات  -

تاریخ انتشار 2011