Precision medicine

Not every patient is the same.
Neither is their cancer.

Tumours of the same name behave differently. Two patients with "breast cancer" can have opposite drug sensitivities, different surgical paths, and very different outcomes. POLEX brings chromosomal-fragility data into that decision.

Why it matters

One drug doesn't fit every patient.

Disease is heterogeneous. Cancer, neurodegeneration, ageing, gene therapy: response varies even when the diagnosis is identical. Oncology shows the principle most starkly. The numbers below are from cancer, but the same logic holds across disease.

30-50%of chemotherapy patients do not respond
15-20%of cancers are HRD, PARPi-sensitive
14%of solid tumors are MSI-H, IO-responsive
~3%of TP53 mutations change treatment

Genomic instability is heterogeneous across tumours. The same drug that cures one patient can be useless in another with the same histology diagnosis. Molecular context changes everything: which chromosomes, which breakpoints, which repair pathways.

The hypothesis

Chromosomes break where they were already fragile.

Cancers have distinct patterns of chromosomal instability. BRCA1/2-deficient tumours break around 17q21 and 13q12. Pancreatic cancers accumulate damage around KRAS on 12p and CDKN2A on 9p. Small-cell lung carcinomas destabilise RB1 on 13q and TP53 on 17p. Ewing sarcomas are defined by the EWSR1-FLI1 t(11;22) fusion.

When you map breaks at base resolution, not just at calling-panel hotspots, these patterns read as clean genomic fingerprints.

Fragile-site signatures

  • FRA3BFHIT · 60% of tumours
  • FRA16DWWOX · breast, prostate, lung
  • 8p21-23Common deletion region
  • 17p13 (TP53)Pan-cancer hotspot
  • 3p21Renal, lung, head & neck
The break atlas

50 cancers, 50 break fingerprints.

Each card shows representative break-burden density, affected chromosomes and genes, drug-class sensitivity, treatment mix, and expected response. Click a category to filter.

Glioblastoma

Mid instability
0100 break burden / Mb
Affected regions
EGFR (7p) · PTEN (10q) · CDKN2A · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx15% Cx55% Combo
Expected response
14%
Relapse90%
5-yr survival7%
Primary Chemo+RT

Thyroid anaplastic

High instability
0100 break burden / Mb
Affected regions
TP53 · BRAF · TERT promoter
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
20% Sx25% Cx55% Combo
Expected response
12%
Relapse85%
5-yr survival5%
Primary Targeted

Pancreatic (PDAC)

High instability
0100 break burden / Mb
Affected regions
KRAS (12p) · TP53 · CDKN2A (9p) · SMAD4 (18q)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
20% Sx55% Cx25% Combo
Expected response
18%
Relapse80%
5-yr survival12%
Primary Chemo

Mesothelioma

Low instability
0100 break burden / Mb
Affected regions
BAP1 (3p21) · NF2 (22q12) · CDKN2A (9p21)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
15% Sx35% Cx50% Combo
Expected response
20%
Relapse80%
5-yr survival10%
Primary Chemo

Small-cell lung

High instability
0100 break burden / Mb
Affected regions
TP53 · RB1 (13q) · MYC family
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
10% Sx65% Cx25% Combo
Expected response
38%
Relapse70%
5-yr survival7%
Primary Chemo

Esophageal adeno

High instability
0100 break burden / Mb
Affected regions
TP53 · SMAD4 · ERBB2 · 8q gain
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx25% Cx45% Combo
Expected response
32%
Relapse70%
5-yr survival20%
Primary Chemo+RT

Adrenocortical

High instability
0100 break burden / Mb
Affected regions
TP53 · CTNNB1 · ZNRF3
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx35% Cx35% Combo
Expected response
22%
Relapse75%
5-yr survival35%
Primary Chemo

Hepatocellular

Mid instability
0100 break burden / Mb
Affected regions
CTNNB1 (3p) · TP53 · ARID1A
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx20% Cx40% Combo
Expected response
30%
Relapse65%
5-yr survival20%
Primary Targeted

Esophageal SCC

Mid instability
0100 break burden / Mb
Affected regions
TP53 · CDKN2A · PIK3CA · SOX2 (3q)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx25% Cx40% Combo
Expected response
35%
Relapse65%
5-yr survival22%
Primary Chemo+RT

MDS high-risk

Mid instability
0100 break burden / Mb
Affected regions
del(5q) · monosomy 7 · del(20q) · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx65% Cx35% Combo
Expected response
35%
Relapse65%
5-yr survival25%
Primary Chemo

AML

Mid instability
0100 break burden / Mb
Affected regions
FLT3 (13q12) · NPM1 (5q35) · chr 5/7 abnormalities
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx60% Cx40% Combo
Expected response
40%
Relapse60%
5-yr survival30%
Primary Chemo

Gastric MSS

Mid instability
0100 break burden / Mb
Affected regions
CDH1 · TP53 · KRAS
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
50% Sx20% Cx30% Combo
Expected response
38%
Relapse55%
5-yr survival32%
Primary Chemo

Soft-tissue sarcoma

High instability
0100 break burden / Mb
Affected regions
TP53 · MDM2 (12q) · CDK4
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
45% Sx25% Cx30% Combo
Expected response
35%
Relapse55%
5-yr survival50%
Primary Chemo

Lung adeno

Mid instability
0100 break burden / Mb
Affected regions
EGFR (7p) · KRAS · TP53 · CDKN2A
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx25% Cx35% Combo
Expected response
52%
Relapse45%
5-yr survival25%
Primary Targeted

Multiple myeloma

Mid instability
0100 break burden / Mb
Affected regions
t(4;14) · t(11;14) · TP53 · MYC
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx55% Cx45% Combo
Expected response
50%
Relapse70%
5-yr survival55%
Primary Targeted

Serous ovarian

High instability
0100 break burden / Mb
Affected regions
TP53 (>95%) · BRCA1/2 · HRD signature
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
25% Sx15% Cx60% Combo
Expected response
70%
Relapse70%
5-yr survival45%
Primary Platinum

Urothelial bladder

High instability
0100 break burden / Mb
Affected regions
TP53 · RB1 · FGFR3 (4p)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx15% Cx50% Combo
Expected response
45%
Relapse55%
5-yr survival55%
Primary IO

Mantle-cell lymphoma

Mid instability
0100 break burden / Mb
Affected regions
CCND1 t(11;14) · TP53 · ATM
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx55% Cx45% Combo
Expected response
55%
Relapse55%
5-yr survival50%
Primary Targeted

HNSCC

Mid instability
0100 break burden / Mb
Affected regions
TP53 · CDKN2A · PIK3CA (3q) · FAT1 (4q)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx20% Cx40% Combo
Expected response
42%
Relapse45%
5-yr survival55%
Primary Chemo+RT

Merkel cell

Mid instability
0100 break burden / Mb
Affected regions
MCV integration · TP53 · RB1 (13q14)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx20% Cx50% Combo
Expected response
50%
Relapse45%
5-yr survival50%
Primary IO

Osteosarcoma

High instability
0100 break burden / Mb
Affected regions
TP53 · RB1 · MDM2 amp
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx35% Cx25% Combo
Expected response
45%
Relapse40%
5-yr survival65%
Primary Chemo

Neuroblastoma

High instability
0100 break burden / Mb
Affected regions
MYCN (2p) amp · 1p del · 17q gain
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
25% Sx30% Cx45% Combo
Expected response
58%
Relapse45%
5-yr survival60%
Primary Chemo

Gastric MSI-H

High instability
0100 break burden / Mb
Affected regions
MLH1 · PIK3CA · ARID1A
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx20% Cx40% Combo
Expected response
55%
Relapse35%
5-yr survival55%
Primary IO

Nasopharyngeal

Mid instability
0100 break burden / Mb
Affected regions
TP53 · EBV integration · 3p21 loss
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
10% Sx30% Cx60% Combo
Expected response
55%
Relapse40%
5-yr survival60%
Primary Chemo+RT

Melanoma

High instability
0100 break burden / Mb
Affected regions
BRAF (7q) · NRAS · CDKN2A
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx15% Cx55% Combo
Expected response
48%
Relapse40%
5-yr survival68%
Primary IO

Cervical

Mid instability
0100 break burden / Mb
Affected regions
p53 (inactivated by HPV E6) · PIK3CA (3q26) · EP300
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
40% Sx25% Cx35% Combo
Expected response
50%
Relapse40%
5-yr survival66%
Primary Chemo+RT

Colorectal MSS

Low instability
0100 break burden / Mb
Affected regions
APC (5q) · KRAS · TP53 · SMAD4
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
55% Sx20% Cx25% Combo
Expected response
48%
Relapse35%
5-yr survival65%
Primary Chemo

Triple-negative BC

High instability
0100 break burden / Mb
Affected regions
TP53 · 8p loss · MYC gain
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx20% Cx50% Combo
Expected response
58%
Relapse40%
5-yr survival65%
Primary Platinum

Chondrosarcoma

Low instability
0100 break burden / Mb
Affected regions
IDH1/2 · COL2A1
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
65% Sx10% Cx25% Combo
Expected response
40%
Relapse30%
5-yr survival75%
Primary Surgery

Renal clear cell

Low instability
0100 break burden / Mb
Affected regions
VHL (3p) · PBRM1 · SETD2 · BAP1
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
50% Sx5% Cx45% Combo
Expected response
50%
Relapse35%
5-yr survival75%
Primary IO

DLBCL

Mid instability
0100 break burden / Mb
Affected regions
BCL2 (18q) · BCL6 (3q) · MYC (8q)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx45% Cx55% Combo
Expected response
62%
Relapse35%
5-yr survival65%
Primary Chemo

Rhabdomyosarcoma

Mid instability
0100 break burden / Mb
Affected regions
PAX3-FOXO1 t(2;13) · MYCN · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx25% Cx40% Combo
Expected response
60%
Relapse35%
5-yr survival70%
Primary Chemo

Follicular lymphoma

Low instability
0100 break burden / Mb
Affected regions
BCL2 t(14;18) · EZH2 · KMT2D
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx40% Cx60% Combo
Expected response
75%
Relapse60%
5-yr survival80%
Primary Targeted

CLL

Low instability
0100 break burden / Mb
Affected regions
13q14.3 del · TP53 (17p) · ATM (11q22.3) · NOTCH1
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
5% Sx70% Cx25% Combo
Expected response
68%
Relapse40%
5-yr survival83%
Primary Targeted

Colorectal MSI-H

High instability
0100 break burden / Mb
Affected regions
MLH1/MSH2/MSH6/PMS2 · BRAF
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx15% Cx50% Combo
Expected response
65%
Relapse22%
5-yr survival72%
Primary IO

Endometrial MSS

Low instability
0100 break burden / Mb
Affected regions
TP53 · CTNNB1 · PPP2R1A
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
60% Sx15% Cx25% Combo
Expected response
58%
Relapse25%
5-yr survival82%
Primary Chemo

Medulloblastoma

Mid instability
0100 break burden / Mb
Affected regions
MYC · MYCN · i(17q) (isochromosome)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
30% Sx20% Cx50% Combo
Expected response
70%
Relapse30%
5-yr survival75%
Primary Chemo+RT

Ewing sarcoma

High instability
0100 break burden / Mb
Affected regions
EWSR1-FLI1 t(11;22) · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx20% Cx45% Combo
Expected response
72%
Relapse30%
5-yr survival75%
Primary Chemo

Endometrial MSI-H

High instability
0100 break burden / Mb
Affected regions
PTEN · PIK3CA · ARID1A · MMR genes
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
50% Sx10% Cx40% Combo
Expected response
62%
Relapse20%
5-yr survival80%
Primary IO

Prostate

Mid instability
0100 break burden / Mb
Affected regions
AR (Xq12) · PTEN (10q23) · TMPRSS2-ERG (21q22)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
50% Sx10% Cx40% Combo
Expected response
55%
Relapse30%
5-yr survival98%
Primary Hormone

HER2+ breast

Mid instability
0100 break burden / Mb
Affected regions
17q12 (ERBB2) · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
45% Sx25% Cx30% Combo
Expected response
64%
Relapse24%
5-yr survival85%
Primary Targeted

Burkitt lymphoma

High instability
0100 break burden / Mb
Affected regions
MYC t(8;14) (variants: t(2;8), t(8;22)) · TP53 · ID3
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx60% Cx40% Combo
Expected response
75%
Relapse20%
5-yr survival70%
Primary Chemo

BRCA1/2 breast

High instability
0100 break burden / Mb
Affected regions
17q21 (BRCA1) · 13q12 (BRCA2) · TP53
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx15% Cx50% Combo
Expected response
72%
Relapse28%
5-yr survival82%
Primary PARPi

GIST

Low instability
0100 break burden / Mb
Affected regions
KIT (4q) · PDGFRA (4q) · SDHB
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
55% Sx10% Cx35% Combo
Expected response
65%
Relapse20%
5-yr survival82%
Primary Targeted

HR+ breast

Low instability
0100 break burden / Mb
Affected regions
PIK3CA · ESR1 · CCND1 (11q13)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
55% Sx20% Cx25% Combo
Expected response
60%
Relapse18%
5-yr survival90%
Primary Hormone

Hepatoblastoma

Low instability
0100 break burden / Mb
Affected regions
CTNNB1 · APC · TERT
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
50% Sx20% Cx30% Combo
Expected response
80%
Relapse20%
5-yr survival80%
Primary Chemo

Hodgkin lymphoma

Low instability
0100 break burden / Mb
Affected regions
JAK-STAT · 9p24 (PD-L1) · REL
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
0% Sx35% Cx65% Combo
Expected response
85%
Relapse20%
5-yr survival88%
Primary IO

Testicular GCT

Mid instability
0100 break burden / Mb
Affected regions
12p gain · TP53 · KIT
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
55% Sx15% Cx30% Combo
Expected response
85%
Relapse15%
5-yr survival95%
Primary Platinum

Wilms tumour

Mid instability
0100 break burden / Mb
Affected regions
WT1 (11p13) · 11p15 (WT2) · 1p/16q · CTNNB1
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx25% Cx40% Combo
Expected response
90%
Relapse15%
5-yr survival92%
Primary Chemo

Retinoblastoma

Low instability
0100 break burden / Mb
Affected regions
RB1 (13q14)
Drug sensitivity
PARPiPlatinumIOChemo
Treatment mix
35% Sx30% Cx35% Combo
Expected response
95%
Relapse10%
5-yr survival96%
Primary Chemo
Beyond oncology

DNA break pathology isn’t only about cancer.

Genetic instability drives neurodegeneration, premature ageing, and immunodeficiency. POLEX’s per-read break signatures translate across all three.

Neurodegeneration

When neurons can't keep up with a lifetime of DNA damage.

Post-mitotic neurons accumulate DNA damage across decades. Defects in DDR signalling, R-loop resolution, or oxidative repair drive distinct clinical syndromes. 15 examples.

ALS (familial)

High severity
0100 break burden / Mb
Affected regions
C9orf72 · SOD1 · FUS · R-loop / DDR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
75% Sym15% Prev10% Cure
Symptom control
18%
Onset40-60 yr
ProgressionRapid
Primary Symptomatic

SCA1 (ATXN1)

High severity
0100 break burden / Mb
Affected regions
ATXN1 polyQ (6p22.3) · Polyglutamine
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
80% Sym15% Prev5% Cure
Symptom control
20%
Onset30-40 yr
ProgressionProgressive
Primary Symptomatic

Aicardi-Goutières

High severity
0100 break burden / Mb
Affected regions
TREX1 · SAMHD1 · RNASEH2 · cGAS-STING
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
70% Sym20% Prev10% Cure
Symptom control
20%
Onset<1 yr
ProgressionRapid
Primary IO/JAK

SCA3 (Machado-Joseph)

High severity
0100 break burden / Mb
Affected regions
ATXN3 polyQ (14q32) · Polyglutamine
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
80% Sym15% Prev5% Cure
Symptom control
22%
Onset20-50 yr
ProgressionProgressive
Primary Symptomatic

AOA2 (SETX)

High severity
0100 break burden / Mb
Affected regions
SETX (9q34) · R-loop / SSB
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
75% Sym20% Prev5% Cure
Symptom control
22%
Onset10-20 yr
ProgressionProgressive
Primary Symptomatic

Ataxia-telangiectasia

High severity
0100 break burden / Mb
Affected regions
ATM (11q22) · DSB repair
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
60% Sym30% Prev10% Cure
Symptom control
25%
Onset<5 yr
ProgressionRapid
Primary Supportive

Huntington disease

High severity
0100 break burden / Mb
Affected regions
HTT CAG (4p16) · Transcription-coupled
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
70% Sym20% Prev10% Cure
Symptom control
30%
Onset30-50 yr
ProgressionProgressive
Primary Symptomatic

Friedreich's ataxia

High severity
0100 break burden / Mb
Affected regions
FXN GAA (9q21.11) · Frataxin
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
65% Sym25% Prev10% Cure
Symptom control
30%
Onset5-25 yr
ProgressionProgressive
Primary Gene-Rx

Frontotemporal dementia

Mid severity
0100 break burden / Mb
Affected regions
MAPT · GRN · C9orf72 · RNA / DDR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
75% Sym20% Prev5% Cure
Symptom control
22%
Onset45-65 yr
ProgressionProgressive
Primary Symptomatic

Alzheimer's (sporadic)

Mid severity
0100 break burden / Mb
Affected regions
APOE4 (19q13) · CLU · TREM2 · APP / PSEN1 (familial) · Oxidative
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
80% Sym15% Prev5% Cure
Symptom control
25%
Onset60+ yr
ProgressionSlow
Primary Symptomatic

Fragile X tremor/ataxia

Mid severity
0100 break burden / Mb
Affected regions
FMR1 premutation (Xq27) · R-loop
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
70% Sym20% Prev10% Cure
Symptom control
25%
Onset60+ yr
ProgressionSlow
Primary Symptomatic

Hereditary spastic paraplegia

Mid severity
0100 break burden / Mb
Affected regions
SPAST · ATL1 · REEP1 · Axonal DDR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
75% Sym20% Prev5% Cure
Symptom control
32%
Onset10-40 yr
ProgressionSlow
Primary Symptomatic

Rett syndrome

Mid severity
0100 break burden / Mb
Affected regions
MECP2 (Xq28) · Chromatin / DDR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
80% Sym15% Prev5% Cure
Symptom control
35%
Onset<2 yr
ProgressionProgressive
Primary Symptomatic

Parkinson's disease

Mid severity
0100 break burden / Mb
Affected regions
SNCA · LRRK2 · PRKN · Mito DDR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
70% Sym20% Prev10% Cure
Symptom control
38%
Onset50+ yr
ProgressionSlow
Primary Symptomatic

Myotonic dystrophy 1

Mid severity
0100 break burden / Mb
Affected regions
DMPK CTG (19q13) · RNA repeat
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
65% Sym25% Prev10% Cure
Symptom control
40%
Onset20-40 yr
ProgressionProgressive
Primary Symptomatic
Premature ageing

Progeroid syndromes: DNA repair, broken at the source.

Helicase loss, NER defects, nuclear lamina disruption. When repair fails in every cell, the body ages decades early. 15 canonical progerias.

Restrictive dermopathy

High severity
0100 break burden / Mb
Affected regions
ZMPSTE24 · LMNA · Nuclear lamina
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
40% Sym40% Prev20% Cure
Symptom control
8%
OnsetAt birth
ProgressionVery rapid
Primary Supportive

Hutchinson-Gilford progeria

High severity
0100 break burden / Mb
Affected regions
LMNA (1q22) · Nuclear lamina
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym30% Prev15% Cure
Symptom control
15%
Onset<2 yr
ProgressionVery rapid
Primary Farnesyl-TI

Nestor-Guillermo progeria

High severity
0100 break burden / Mb
Affected regions
BANF1 (11q13) · Nuclear envelope
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym30% Prev15% Cure
Symptom control
15%
Onset<5 yr
ProgressionRapid
Primary Supportive

Wiedemann-Rautenstrauch

High severity
0100 break burden / Mb
Affected regions
POLR3A · RNA Pol III
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
60% Sym30% Prev10% Cure
Symptom control
15%
OnsetAt birth
ProgressionRapid
Primary Supportive

Cockayne syndrome A

High severity
0100 break burden / Mb
Affected regions
ERCC8 (5q12) · TC-NER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
60% Sym30% Prev10% Cure
Symptom control
18%
Onset<2 yr
ProgressionRapid
Primary Supportive

Cockayne syndrome B

High severity
0100 break burden / Mb
Affected regions
ERCC6 (10q11) · TC-NER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
60% Sym30% Prev10% Cure
Symptom control
18%
Onset<2 yr
ProgressionRapid
Primary Supportive

Seckel syndrome

High severity
0100 break burden / Mb
Affected regions
ATR (3q23) · CENPJ · DDR / rep stress
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
60% Sym30% Prev10% Cure
Symptom control
20%
OnsetAt birth
ProgressionProgressive
Primary Supportive

Xeroderma pigmentosum A

High severity
0100 break burden / Mb
Affected regions
XPA (9q22) · GG-NER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
50% Sym40% Prev10% Cure
Symptom control
22%
Onset<5 yr
ProgressionProgressive
Primary Preventive

Nijmegen breakage syn.

High severity
0100 break burden / Mb
Affected regions
NBN (8q21) · MRN / DSB
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym30% Prev15% Cure
Symptom control
22%
Onset<2 yr
ProgressionProgressive
Primary Supportive

Werner syndrome

High severity
0100 break burden / Mb
Affected regions
WRN (8p12) · HR / replication
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym30% Prev15% Cure
Symptom control
25%
Onset20-30 yr
ProgressionRapid
Primary Supportive

Xeroderma pigmentosum C

High severity
0100 break burden / Mb
Affected regions
XPC (3p25) · GG-NER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
50% Sym40% Prev10% Cure
Symptom control
25%
Onset<10 yr
ProgressionProgressive
Primary Preventive

Bloom syndrome

High severity
0100 break burden / Mb
Affected regions
BLM (15q26) · HR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym30% Prev15% Cure
Symptom control
28%
Onset0-5 yr
ProgressionProgressive
Primary Supportive

Rothmund-Thomson

High severity
0100 break burden / Mb
Affected regions
RECQL4 (8q24) · Replication / HR
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym35% Prev10% Cure
Symptom control
30%
Onset<2 yr
ProgressionProgressive
Primary Supportive

Trichothiodystrophy

Mid severity
0100 break burden / Mb
Affected regions
ERCC2 · ERCC3 · GTF2H5 · NER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
65% Sym25% Prev10% Cure
Symptom control
30%
Onset<1 yr
ProgressionProgressive
Primary Supportive

Xeroderma pigmentosum V

Mid severity
0100 break burden / Mb
Affected regions
POLH / XPV (6p21) · TLS
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
55% Sym35% Prev10% Cure
Symptom control
40%
Onset10-30 yr
ProgressionSlow
Primary Preventive
Immunodeficiency

When V(D)J breaks don’t resolve, immunity doesn’t form.

Lymphocyte diversity depends on programmed double-strand breaks. Cells break the DNA deliberately and rejoin it. Failures in NHEJ, class-switch, or ICL repair produce severe immune phenotypes. 15 cases.

Ataxia-telangiectasia

High severity
0100 break burden / Mb
Affected regions
ATM (11q22) · DSB signalling
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
50% Sym35% Prev15% Cure
Symptom control
30%
Onset<5 yr
ProgressionProgressive
Primary Supportive

Bloom syndrome

High severity
0100 break burden / Mb
Affected regions
BLM (15q26) · HR / replication
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
45% Sym35% Prev20% Cure
Symptom control
35%
Onset<5 yr
ProgressionProgressive
Primary Supportive

Fanconi anaemia

High severity
0100 break burden / Mb
Affected regions
FANC-A/C/G/D2 · ICL (FA)
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
40% Sym35% Prev25% Cure
Symptom control
38%
Onset<10 yr
ProgressionProgressive
Primary Bone-marrow-Tx

Nijmegen breakage syn.

High severity
0100 break burden / Mb
Affected regions
NBN (8q21) · MRN / DSB
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
30% Sym35% Prev35% Cure
Symptom control
40%
Onset<2 yr
ProgressionProgressive
Primary Supportive

ATLD (MRE11 def.)

High severity
0100 break burden / Mb
Affected regions
MRE11A (11q21) · MRN
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
30% Sym40% Prev30% Cure
Symptom control
40%
Onset2-5 yr
ProgressionProgressive
Primary Supportive

RIDDLE syndrome

High severity
0100 break burden / Mb
Affected regions
RNF168 (3q29) · Ubiquitin DSB
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
30% Sym40% Prev30% Cure
Symptom control
42%
Onset<5 yr
ProgressionProgressive
Primary Supportive

Ligase IV syndrome

High severity
0100 break burden / Mb
Affected regions
LIG4 (13q33) · NHEJ ligation
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
25% Sym35% Prev40% Cure
Symptom control
45%
Onset<2 yr
ProgressionProgressive
Primary Supportive

Cernunnos/XLF def.

High severity
0100 break burden / Mb
Affected regions
NHEJ1 (2q35) · NHEJ ligation
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
20% Sym35% Prev45% Cure
Symptom control
50%
Onset<2 yr
ProgressionProgressive
Primary Bone-marrow-Tx

DNA-PKcs deficiency

High severity
0100 break burden / Mb
Affected regions
PRKDC (8q11) · NHEJ / DNA-PK
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
20% Sym30% Prev50% Cure
Symptom control
55%
Onset<1 yr
ProgressionRapid
Primary Bone-marrow-Tx

Artemis SCID

High severity
0100 break burden / Mb
Affected regions
DCLRE1C (10p13) · NHEJ hairpin
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
15% Sym25% Prev60% Cure
Symptom control
65%
Onset<1 yr
ProgressionRapid
Primary Bone-marrow-Tx

SCID — RAG1 deficiency

High severity
0100 break burden / Mb
Affected regions
RAG1 (11p13) · V(D)J
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
10% Sym25% Prev65% Cure
Symptom control
70%
Onset<1 yr
ProgressionRapid
Primary Bone-marrow-Tx

SCID — RAG2 deficiency

High severity
0100 break burden / Mb
Affected regions
RAG2 (11p13) · V(D)J
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
10% Sym25% Prev65% Cure
Symptom control
70%
Onset<1 yr
ProgressionRapid
Primary Bone-marrow-Tx

XLP / SH2D1A

Mid severity
0100 break burden / Mb
Affected regions
SH2D1A (Xq25) · Immune signalling
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
25% Sym40% Prev35% Cure
Symptom control
65%
OnsetChildhood
ProgressionVariable
Primary Bone-marrow-Tx

Hyper-IgM Type 5 (UNG)

Mid severity
0100 break burden / Mb
Affected regions
UNG (12q24) · BER
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
20% Sym35% Prev45% Cure
Symptom control
72%
Onset2-5 yr
ProgressionSlow
Primary IgG replacement

Hyper-IgM Type 2 (AID)

Mid severity
0100 break burden / Mb
Affected regions
AICDA (12p13) · Class-switch
Therapeutic approach
Gene-RxBMTTargetedSupportive
Care pattern
20% Sym30% Prev50% Cure
Symptom control
75%
Onset2-5 yr
ProgressionSlow
Primary IgG replacement
Signal → diagnosis

POLEX as a diagnostic marker.

Our output is not a disease label. It is a quantitative fingerprint that places a tumour on a continuous axis of chromosomal fragility. Where on that axis a patient sits informs which drugs, which dose, which monitoring cadence.

PREDICT

HRD probability

From per-read break signatures, estimate homologous-repair deficiency in minutes. No reflex panel wait.

STRATIFY

Drug sensitivity score

A single score per drug class (PARPi, platinum, IO, targeted) from the fragility fingerprint.

MONITOR

Repair kinetics

Track break accumulation across time points. Early signal for resistance, progression, or repair failure.

STAGE

Chromosomal fragility index

A reproducible, quantitative marker that can stratify clinical trials and standardise cross-study comparisons.

Want to pilot POLEX in your clinic or study?

We run sample pilots with clinical investigators and pharmaceutical partners. Typical turnaround from sample to break atlas is seven days.

Start a pilot conversation →

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