A reinvestigation of somatic hypermethylation at the PTEN CpG island in cancer cell lines.

[cowden syndrome]

PTEN is an important tumour suppressor gene that is mutated in Cowden syndrome as well as various sporadic cancers . CpG island hypermethylation is another route to tumour suppressor gene inactivation , however , the literature regarding PTEN hypermethylation in cancer is controversial . Furthermore , investigation of the methylation status of the PTEN CpG island is challenging due to sequence homology with the PTEN pseudogene , PTENP 1 . PTEN shares a CpG island promoter with another gene known as KLLN . Here we present a thorough reinvestigation of the methylation status of the PTEN CpG island in DNA from colorectal , breast , ovarian , glioma , lung and haematological cancer cell lines .U sing a range of bisulphite-based PCR assays we investigated 6 regions across the PTEN CpG island . We found that regions 1 -4 were not methylated in cancer cell lines (0 /36 ). By allelic bisulphite sequencing and pyrosequencing methylation was detected in regions 5 and 6 in colorectal , breast and haematological cancer cell lines . However , methylation detected in this region was associated with the PTENP 1 promoter and not the PTEN CpG island .We show that methylation of the PTEN CpG island is a rare event in cancer cell lines and that apparent methylation most likely originates from homologous regions of the PTENP 1 pseudogene promoter . Future studies should utilize assays that reliably discriminate between PTEN and PTENP 1 to avoid data misinterpretation .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated